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PROMISE&PROGRESS

ENGINEERINGCURES

Physicians and Engineers Working Together to Fight Cancer

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T H E S I D N E Y K I M M E L C O M P R E H E N S I V E C A N C E R C E N T E R A T J O H N S H O P K I N S

PROMISE&PROGRESS

T H E S I D N E Y K I M M E L C O M P R E H E N S I V E C A N C E R C E N T E R A T J O H N S H O P K I N S

ENGINEERINGCURES

Physicians and Engineers Working Together to Fight Cancer

Promise & Progress is published by The Sidney Kimmel ComprehensiveCancer Center at Johns HopkinsOffice of Public Affairs901 South Bond StreetSuite 573Baltimore, Maryland 21231(410) 955-1287

William G. Nelson, M.D., Ph.D.Director

Amy MoneDirector of Public Affairs

Valerie Matthews MehlEditor and Sr. [email protected]

Michelle Potter, Lauren Small, and Vanessa WastaContributing Writers

Michelle Potter and Shaun MorrisEditorial Assistants

Larry Canner, Jon Christofersen,Fred Dubs, Homewood Photo,Marty Katz, Will Kirk, Joe Rubino,and Keith WellerPhotography

Steven RossmanCopy Editor

MSK Partners, Inc.Design + Production

PROMISE&PROGRESS

10Engineering CuresEngineers are bringing new technologies to fight against cancer. Working with researchers at the Kimmel Cancer Center, they are helpingmake new personalized cancer therapies a reality for patients like Jerry Morton.

Headline MakersThe latest research from

the Kimmel Cancer Center

including new discoveries

in cancer genetics and

“microbeads” that fight

liver cancer.

In The NewsNoteworthy progress,

new appointments, and

other cancer news.

PhilanthropyGifts and donations that

are funding our cancer

research and advancing

clinical care.

C O N T E N T S O N T H E W E B

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On the Cover: This robot, developed by engineer Dan Stoianovici,

is used to treat prostate cancer.

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© 2011 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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12011/2012 PROMISE&PROGRESS

JOHNS HOPKINS is uniquely positioned to make revolutionaryadvances against diseases, like cancer. Advances that could not even be imagined 10 to 15 years ago are now happening. I am proud to tell you that our researchers have been at thecenter of these amazing accomplishments.

For certain, we are doing things a bit differently now. We are transforming cancer medicine away from a model in whichwe see patients for the first time when they begin experiencingsymptoms to one that detects, manages, and many times eradicates cancers before patients even know they have them.This new system, driven in large part by our pioneering discoveries in cancer genetics and epigenetics, is one that preserves health by preventing cancers, very accurately predicting who will get them, and personalizing treatments to each individual patient, making sure he or she gets the treat-ments that will work against the unique cellular characteristicsof the cancer.

As you will read in this issue of Promise & Progress, we have a new partner in this work. Researchers in the Whiting School of Engineering, long recognized for using the principles of engineering to fight human diseases, are now working side byside with cancer researchers and clinicians to improve the toolswe use to make progress in the laboratory and at the bedside.Robotics and other surgical devices, computational and computersciences, nanobiotechnology, molecular imaging, and other vitalengineering-based expertise and advances are helping us achieveour mission to best prevent, detect, treat, and monitor cancer.

As a result of these and other collaborations, we are alreadyusing scientific discoveries to guide our clinical care. These discoveries are helping to ensure we get the right treatments tothe right people at the right time.

The Kimmel Cancer Center is an incrediblediscovery engine, and our brilliant team ofinvestigators and clinicians has led the way indeveloping tests that detect cellular alterationsthat identify cancers, predict which therapiesthey will respond to, and monitor them forrecurrence. Our success is being fueled by generous support such as that received fromthe Commonwealth Foundation for CancerResearch and David H. Koch. The Common-wealth Foundation gift is allowing us to createthe Center for Personalized Cancer Medicine(see page 36), and the Koch Cancer ResearchBuilding is home to our next generationsequencing laboratory, which is essential toour breakthrough research in cancer biologythat makes personalized therapies possible.

The next step is to adapt these technologiesso that they can be used routinely to makeclinical decisions about how to best treat cancers,not just at the Kimmel Cancer Center, but atcancer centers and hospitals around the world.

We are ushering in a new era of cancermedicine.

William G. Nelson, M.D., Ph.D.Marion I. Knott Professor and DirectorThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

“WE ARE TRANSFORMING CANCERMEDICINE AWAY FROM A MODELIN WHICH WE SEE PATIENTS FORTHE FIRST TIME WHEN THEY BEGINEXPERIENCING SYMPTOMS TOONE THAT DETECTS, MANAGES,AND MANY TIMES ERADICATESCANCERS BEFORE PATIENTS EVEN KNOW THEY HAVE THEM.”

D I R E C T O R ’ S L E T T E R

A NEW ERA IN CANCER MEDICINE

2 PROMISE&PROGRESS 2011/2012

HEADLINE MAKERSTHE LATEST RESEARCH from the JOHNS HOPKINS KIMMEL CANCER CENTER

GENETIC DISCOVERIESIN HEAD AND NECKAND BRAIN CANCERSSCIENCEGenetic sequencing offers powerful cluesto understanding the function of variousgenes and their roles in cancer, andKimmel Cancer Center investigators haveproduced some of the most seminal find-ings in cancer genetics.

Cancers are not “one size fits all” as thediscoveries of Nickolas Papadopoulos,Ph.D., Kenneth Kinzler, Ph.D., and BertVogelstein, M.D., and their research team

have revealed. As a result, therapies cannotbe one size fits all either. Their work inmapping the diverse genetic landscape ofdozens of cancers is leading to prevention,early detection, and treatment strategiespersonalized to target the unique cellularcharacteristics of each individual patient’scancer. In the coming years, thisapproach is expected to revolutionizecancer therapy, improving outcomes bygiving clinicians the information theyneed to deliver the right therapies tothe right patients and to monitor, inreal time, whether or not new target-specific drugs are blocking the cellular

malfunctions now known to be causedby genetic alterations.

These researchers have recentlysequenced the cancer genomes of two moremalignancies—head and neck cancer and abrain cancer known as oligodendroglioma.

HEAD AND NECK CANCER GENOMELittle was known about the genetic causesof head and neck cancers, and this newresearch revealed mutations in two genes,NOTCH 1 and FBXW7, never before associ-ated with the cancer. In a surprising twist,the researchers found that NOTCH 1, identified as a cancer cell growth-promotingoncogene in blood and bone marrow cancers, is a malfunctioning tumor suppressor gene in head and neck cancers.“The mutational analysis of NOTCH clearlyindicated the power of genetic changesdetermining the function of these genes,”says Papadopoulos. This key findingdemonstrates that genes are not presetto be either oncogene or suppressorgene, as previously thought, but insteadtheir roles can vary among tumor typesdepending upon mutations. The samegene can act as a cancer growth promoter insome cases and as a growth suppressor inothers, say the experts.

Their mutational analysis also confirmedprevious findings by Kimmel Cancerinvestigators who in 2000 linked theHuman papillomavirus (HPV) to head andneck cancers and classified it as a uniquesubset of head and neck cancer with itsown biology and associated with animproved prognosis. The researchersuncovered the reason for the improvedoutcomes, finding four times fewer muta-tions in HPV-related cancers than non-HPV-related cancers and no mutationsto the common cancer-related p53 gene.

Another environmental risk factor, cigarette smoking, was associated withmarkedly increased numbers of mutations.Tumors from head and neck cancerpatients with a history of smoking hadtwice as many mutations as tumors fromnon-smokers.

Researchers will now work to decipherthe function of the genes discovered andpotential ways to target them therapeutically.

The discoveries of Kenneth Kinzler (left), Bert Vogelstein (center),and Nickolas Papadopoulos (right) have shown that cancers are not"one size fits all". As a result, therapies cannot be either.


OLIGODENDROGLIOMA BRAIN CANCERResearchers have long known that up to70 percent of oligodendrogliomas arecharacterized by a fusion of two chromo-somes that results in the loss of manygenes. What had eluded scientists, untilnow, were the specific mutated genes that allowed the cancer to develop. After sequencing this cancer, one that typically strikes younger people in theirthirties and forties, the Kimmel CancerCenter team solved the mystery by uncovering mutations to two genes,CIC and FUBP 1. Two-thirds of the tumorsamples studied contained mutations inthese genes. “Whenever we find genesmutated in a majority of tumors, it is likelythat the pathway regulated by that gene iscritical for cancer development and thebiology of the tumor,” says Kinzler.

The research team also found mutationsin the PIK3CA gene, which has been wellstudied in cancer and is already the focusof several clinical trials of targeted therapies.As a result of these findings, scientists suspect that oligodendroglioma patientswith PIK3CA mutations could potentiallybenefit from these experimental therapiesand may be included in these clinical trials.

“Knowing the genetic roadmap of acancer is the key to attacking it,” saysKinzler. Having identified these key genemutations, investigators can now focus ondetermining at what point in the cancerprocess they occur, whether they guideprognosis, and if they might be good targetsfor treatment.

The oligodendroglioma research wasfunded by the Virginia and D.K. LudwigFund for Cancer Research, the Pediatric BrainTumor Foundation, the Duke ComprehensiveCancer Center Core, the Burroughs WellcomeFund, The James S. McDonnell Foundation,state funding from Sao Paulo (FAPESP), theNational Cancer Institute, and the NationalInstitutes of Health.

Editor’s Note: Under agreements betweenthe Johns Hopkins University, Genzyme, ExactSciences, Inostics, Qiagen, Invitrogen, andPersonal Genome Diagnostics, Papodopoulos,Vogelstein, and Kinzler are entitled to a share ofroyalties received by the University on sales of

products related to genes and technologiesdescribed in this article. These researchers areco-founders of Inostics and Personal GenomeDiagnostics, are members of their ScientificAdvisory Board, and own Inostics and PersonalGenome Diagnostics stock, which is subject to restrictions under Johns Hopkins University policy.

IN BRAIN CANCERS,TWO OR MORE TARGETSARE BETTER THAN ONEClinical Cancer Research, December 15, 2010

Brain cancers represent one of the mostdifficult types of cancer to manage. Tumorsthat respond initially to treatment eventu-ally become resistant. Now, research byCharles Eberhart, M.D., Ph.D., revealsnew clues about how cancer gene path-ways conspire to circumvent therapy.

Similar to a computer network thatincreases its computing capabilities bylinking several computers together,groups of genes work together throughpathways to enhance cell function. Cancercells manipulate these pathways to drivetumor growth and spread.

Research by Eberhart and team revealsthat inhibiting a single cancer cell develop-

ment pathway withdrug therapy can disruptand may actuallyincrease activity in otherpathways and raise therisk of tumors becomingresistant to therapy.

The team found that genes involved in onepathway interacted directly with genes inanother pathway. “Our research indicatesthat it may be necessary to simultane-ously target multiple development signaling pathways to prevent cancerfrom becoming resistant to therapy,”says Eberhart. “A single agent is not likelyto work for prolonged periods.”

Eberhart and team studied an agentthat targets and blocks a known cancergene pathway called Notch in glioblastomabrain cancer cell lines. They found that when they inhibited Notch, activityincreased in two other common cancer

development pathways known as Hedgehogand Wnt. Eberhart speculates that tumorscompensate for therapy directed at onepathway by turning on a different one.Combining the Notch inhibitor with a second drug to also block Hedgehog dramatically decreased cell growth, by asmuch as 90 percent, in the cell line studies.The combined approach had an antitumoreffect, increasing natural cell death and hindering cells’ ability to form clusters orcolonies. They achieved similar results inlaboratory studies using human glioblas-toma samples removed during surgery.

Glioblastoma is one of the most aggressivetypes of brain cancer. Even when tumors initially respond to treatment, they almostalways eventually become resistant. As aresult, most patients die within two yearsof diagnosis. This research may help expertsbetter understand the cellular mechanismsthat make the cancer so deadly.

Clinical trials evaluating Notch andHedgehog inhibitors in several types of cancer are now under way at the KimmelCancer Center and other cancers centersacross the U.S.

The research was funded by the NationalInstitutes of Health, the Brain Tumor FundersCollaborative, the American Cancer Society,and a National Cancer Institute Brain TumorSPORE grant.

PANCREAS CANCERTIMELINE REVEALSAMPLE TIME FOREARLY INTERVENTION Nature, October 28, 2011

Kimmel Cancer Center and Sol GoldmanPancreatic Cancer Research Center inves-tigators have developed a mathematicalmodel that allows clinicians, for the firsttime, to quantify the development of pan-creas cancer and how best to treat it. Theirwork disproved common scientific thoughtthat this type of cancer progresses to adeadly stage very early in its development.

To the contrary, the research team calculated that it takes an average of 11 years before a cancer cell arises froma precancerous pancreas lesion. Still

Eberhart


HEADLINE MAKERS

spread and applied their findings to mathe-matical models to create a timeline of progression from precancerous lesion todeadly, metastatic disease.

The research was funded by the NationalInstitutes of Health, the Bill and MelindaGates Foundation, the Uehara MemorialFoundation, The AACR-Barletta Foundation,the John Templeton Foundation, the SolGoldman Pancreatic Cancer ResearchCenter, the Michael Rolfe Pancreatic CancerFoundation, the George Rubis Endowmentfor Pancreatic Cancer Research, the Joseph C.Monastra Foundation for Pancreatic CancerResearch, the Alfredo Scatena MemorialFund, Sigma Beta Sorority, the Skip ViraghFoundation, the Virginia and D.K. LudwigFund for Cancer Research, the Joint Programin Mathematical Biology, and J. Epstein.

CELL CYCLE CLOCKLINKED TO CHILDHOODCANCERSImmunity, February 24, 2011

Researchers linked a molecular cell cycle“clock” which regulates the timing of howDNA is broken up and copied to formnew immune genes to chromosomalabnormalities found in children withleukemia and lymphoma, cancers thatoriginate in immune system cells.

This regulatory function manages howDNA segments are split off and thenreshuffled inside dividing immune cells in a process known as recombination. It is an exceedingly complex biologicalprocess that occurs repeatedly as cellsdivide. In the time it takes to read thissentence, about 10 million recombinationevents will occur inside the human body.Although most of the time they occurseamlessly, the sheer numbers mean thatpotential mismatches of genetic bits couldlead to genetic rearrangements that maywreak havoc in the immune system andsometimes lead to cancer.

“We are exposed to the possibilityof cancer every time we make a newimmune cell,” says Stephen Desiderio,M.D., Ph.D., director of the Institute forBasic Biomedical Sciences, the Institutefor Cell Engineering Immunology

Program, and a Kimmel Cancer Centerinvestigator. “One of the many safeguardsin place to ensure that this doesn’t happenappears to be a cellular clock that timesthese potentially dangerous events andregulates them.

Desiderio and team’s work focused ona molecular knife—a gene called Rag2—that chops up DNA inside of immune system cells. Rag2 is normally availableduring a precise window of time duringthe cell cycle and then cleared away toensure proper DNA assembly. Desiderioand team showed that if Rag2 is mutatedand does not become disabled before DNAreplication, it could chop the wrong geneticmaterial at the wrong places and wrongtimes. The result is strange bits joinedtogether in odd ways causing abnormalchromosomes, like those seen in childrenwith leukemia and lymphoma, to occur.

“Knowing the underlying mutationsthat make it more likely for a child to getthese chromosomal abnormalities couldmean, at the very least, we might be ableto identify children at risk and watchthem more closely,” says Desiderio.“Perhaps in the future, the knowledgecould lead to new therapies.”

The research was funded by the NationalCancer Institute and a gift to the Institute forCell Engineering

another seven years may pass as thatcancer grows to form a tumor, giving at least one cell the potential to breakaway and spread the cancer outside ofthe pancreas in a process known as metastasis. This spread represents a lethalturning point in the progression of the cancer, and once it occurs, the research teamreports that these patients die, on average,two and half years later.

While the research reveals a large win-dow of time before a pancreas cancer turnsdeadly, currently, “pretty much everybodyis diagnosed after that window has closed,”says pancreas cancer expert ChristineIacobuzio-Donahue, M.D., Ph.D.New, early diagnostic tests to detectthese cancers during this 11 to 18 yearwindow would provide an opportunityto intervene and potentially cure thesecancers with surgery investigators say.Their goal is to create a screening method,similar to those used to screen for breast

and colon cancers, to detect very earlypancreas cancers, long before

they cause symptoms.Iacobuzio-Donahue suggests that just ascolonoscopies are used to look inside the colon

for precancerous lesionscalled polyps, physicians

could use a similar techniquecalled endoscopy, which uses an endoscopeinserted through the mouth, to examine the pancreas for precancerous lesions.

To make their calculations, the teamstudied tissue collected at autopsy fromseven patients who died of metastatic pan-creas cancer. A team led by Bert Vogelstein,M.D., the world’s foremost expert in deciphering the genetic blueprints of cancer, identified and classified the geneticalterations in each patient’s pancreas tumorand the sites to which it spread. In all of thepatients, the investigators found similarmutations in both the originating tumorand the body sites where it spread, geneti-cally linking the metastatic lesions to theoriginal pancreas tumor from which itarose. They classified mutations thatoccurred prior to metastasis and those that happened after the cancer began to

Desiderio

CELLS MANIPULATED TOREPAIR DISEASED LIVERScience Translational Medicine, May 11, 2011

In work that could one day help peoplewith liver cancer, researchers returneda variety of adult human cells, includingliver, bone marrow, and skin cells, toan embryonic state. In animal models,these cells took root in the liver andregenerated damaged tissue.

This early science may provide a foun-dation for producing functional liver cellsfor patients who have liver diseases andneed transplants, says Yoon-Young Jang,M.D., Ph.D., the Kimmel Cancer Centerscientist who led the study. The liver isone of the few organs that naturallyregenerates damaged tissue, but Jang saysthat certain diseases, including cancer,eventually destroy this natural ability.

Currently, the only option for manypatients is to receive a new liver or livercell transplant. Transplantation relies onthe availability of donor liver tissue, andmature liver cells, she says, are difficult toisolate or grow in the laboratory. “Ourfindings could be applied clinically as analternative to liver transplant, overcomingthe problem of long waiting lists fororgans and concerns about immune system rejection of donated tissue,” saysJang. The cells Jang used in her researchcan be made from a tiny amount of manykinds of tissue and can be grown indefi-nitely in the laboratory.

The research uses induced-pluripotentstem cells (iPSCs), cells that are madefrom adult cells and genetically repro-grammed to revert to an embryonic stemcell-like state, with the ability to transforminto different cell types. Jang and teamgenerated iPSCs from a variety of adulthuman cells, including liver cells, bonemarrow stem cells, and skin cells. Whileall of the cells were molecularly similar toeach other, they retained a distinctive sig-nature inherited from the cell from whichthey originated. Still, Jang and team wereable to induce the cells, regardless of theirorigin, to differentiate into liver cells.

Jang says additional studies are neededbefore clinical trials can begin. By nature

of their role to form new cells, the iPSCsintrinsically have the potential to causetumors, and though no tumors developedin the animal studies, Jang and team areconducting ongoing research to ensurethey are stable.

The research was funded by the NationalInstitutes of Health and the Maryland StemCell Research Fund.

DUAL APPROACHBETTER FOR LIVER CANCERThe Journal of Clinical Oncology

A combined treatment for liver cancer thatuses one oral drug and another delivereddirectly to tumors via tiny drug-filledmicrobeads could potentially improveoutcomes for patients with these fast-growing and often deadly tumors.

Both the oral drug, sorafenib, and theone used in the microbeads, doxorubicin,have been approved individually for livercancer treatment. Investigators are hope-ful that combining them through thisnovel delivery method could make treat-ment more effective against liver cancer,

which is seeing increased incidence in theUnited States.

“Both therapies have increased survivalrates in advanced liver cancer, and combining them may push those survivalrates further,” says interventional radiol-ogist and study leader Jean-FrancoisGeschwind, M.D. He and his team treat-ed 35 patients, using the oral drug to blockthe formation of blood vessels that nourishtumors and the microbeads to provideprolonged delivery of an anticancer drugdirectly to the tumor.

Geschwind used a method known aschemoembolization, using a tiny catheter,the size of a single hair, inserted into thetumor to deliver approximately 200,000cancer-drug filled microbeads. For three or more weeks, the drug seeps out of themicrobeads to attack cancer cells. Geschwind,surgeon Timothy Pawlick, M.D., medicaloncologist David Cosgrove, M.D., and


Geschwind

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collaborators believe this dual approachcould prolong the antitumor effects ofchemoembolization.

Liver cancer tends to grow rapidlywithout causing noticeable symptoms. Asa result, Geschwind says it is inoperableby the time most patients are diagnosed,offering a dismal survival outlook of lessthan a year. In these patients, he says,chemoembolization can often increasesurvival by as much as 10 to 15 months.

Clinical studies of chemoembolization,with and without the oral drug, are ongoing.“We're on the path to improving the stan-dard of care for liver cancer," says Geschwind.

This study was funded by BayerHealthCare and Onyx Pharmaceuticals,which manufactures sorafenib, andBiocompatibles, makers of the microbeads.Geschwind and Pawlick are consultants toBayer HealthCare Pharmaceuticals, andGeschwind is a consultant to Biocompatibles.The terms of these arrangements are beingmanaged by The Johns Hopkins University inaccordance with its conflict-of-interest policies.

GENETIC CAUSES OF A TYPE OF PANCREASCANCER UNCOVEREDScience Express, January 20, 2011

Kimmel Cancer Center researchers in theLudwig Center have once again piecedtogether the genetic puzzle of a cancer,this time deciphering the genetic causes of a type of pancreas cancer known asneuroendocrine or islet cell tumors.

This is the latest work from the teamwho has led the world in uncovering thegenetic causes of dozens of cancers,including colon, breast, brain, pancreas,and head and neck cancers.

In this cancer, researchers uncov-ered a unique genetic code specific to each patient that predicts howaggressive the disease is and howwell it will respond to specific treat-ments. “This tells us that it may bemore useful to classify cancers bygene type rather than organ or celltype,” says Nickolas Papadopoulos,Ph.D., director of translational genetics.

Pancreatic neuroendocrine tumorsmake up about five percent of all pancreascancers. Some of these tumors producehormones that leave telltale biologicalsigns of their existence, including changesin blood sugar levels, weight gain, andrashes. Hormone-free tumors do not produce these signs making them difficultto detect and difficult to distinguish fromother types of pancreas cancers.

To better understand how these stealthtumors develop and grow, the investiga-tors studied 68 non-hormonal pancreaticneuroendocrine tumors. Their workrevealed several common gene mutations,including two genes that had not beenpreviously linked to cancer. In addition,they found that patients whose tumorscontained mutations in three genes, calledMEN-1, DAXX, and ATRX, survived atleast 10 years after diagnosis while morethan 60 percent of people whose tumorsdid not have the mutations, died withinfive years of diagnosis. The team alsofound mutations to a family of genescalled mTOR in about 14 percent oftumors that they believe would be goodtargets for personalized therapy. Patientswhose tumors contain alterations tomTOR would be candidates for treatmentwith agents that inhibit these genes, saysPapadopoulos.

The research was funded by the Caring forCarcinoid Foundation, the LustgartenFoundation for Pancreatic Cancer Research,the Sol Goldman Pancreatic Cancer ResearchCenter, the Joseph Rabinowitz Fund forPancreatic Cancer Research, the Virginiaand D. K. Ludwig Fund for Cancer Research,the Raymond and Beverly Sackler ResearchFoundation, the AACR Stand Up to Cancer’sDream Team Translational Cancer ResearchGrant, and the National Institutes of Health.

Editor’s Note: Papadopoulos and othermembers of the research team are co-foundersand members of the scientific advisory boardof Inostics, a company developing technolo-gies for the molecular diagnosis of cancer.

ANTIFUNGAL DRUGWORKS AGAINSTPROSTATE CANCERThe American Society of Clinical OncologyAnnual Meeting, June 2011

A drug used to treat nail fungusappears to keep prostate cancer incheck. In a study of the oral antifungal,called itraconazole, researchers found that it helped some men with advancedprostate cancer, keeping their cancer stable, delaying progression and the needfor chemotherapy.

Forty-six men with prostate cancerswhich had spread to other organs andwho were not responding to hormone

therapy (the standardcourse of treatment formetastatic prostate cancer) were treated witheither low or high dosesof itraconazole. Whilelow doses had minimal

effect, the high dose treatment led to stable or declining levels of PSA (prostatespecific antigen), a prostate cancer marker,in 11 of 24 men who received it.

Kimmel Cancer Center researcherEmmanuel Antonarakis, M.D., led theteam that came upon the drug and itsanticancer potential when reviewing adatabase of more than 3,000 FDA-approved drugs. In laboratory tests byJun Liu, Ph.D., the drug was able toshrink human prostate tumors implantedin mice. It appears to work by blockingtumor vessel blood growth and disruptinga main cancer-initiating gene pathwaycalled Hedgehog.

Antonarakis and team are planninglarger studies of the high-dose itraconazoletherapy.

This research was funded by theDepartment of Defense Prostate CancerResearch Program, the CommonwealthFoundation for Cancer Research, the DavidH. Koch Charitable Foundation, a 2009American Society of Clinical Oncology YoungInvestigator Award granted to Antonarakis,and the National Cancer Institute.


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Antonarakis


EFFECTIVENESS OFHALF-IDENTICALTRANSPLANTSCONFIRMEDThe results of two clinical trials found thatbone marrow or blood stem cell transplantsusing half-matched bone marrow or umbil-ical cord blood are comparable to fullymatched marrow. The finding means thatnearly all patients in need of a transplantcan find donors, says bone marrow trans-plant researcher Ephraim Fuchs, M.D.,who helped develop half-match, or half-identical, (haploidentical) transplants.

Bone marrow transplantation is a poten-tially curative therapy for cancers of theblood and immune cells, such as leukemiaand lymphoma. Although patients andphysicians may seek donors throughnational registries, frequently no match isfound, and the search can take weeks tomonths, time that delays treatment andallows the cancer progress. “People aredying waiting for matched donors from aregistry,” says Fuchs.

He began is research of halploidentical,or half-identical, transplants as an optionfor these patients. Half-identical matchesare parents, children, and most siblings,

so virtually everypatient has a suitabledonor. To make itwork, however, heand his team had tocircumvent a lifethreatening compli-cation, known asgraft versus host disease (GVHD), that occurs whenthe donor immune

system sees its newhost as a foreign

invader and launches an attack against the patient’s tissue and organs. Fuchs andteam pioneered a post-transplant therapy, using the drug cyclophosphamide, thatreprograms the immune system and prevents severe GVHD.

With the ability to safely perform half-identical transplansts and evidence thatthey are as clinically effective as fullmatches, the treatment will likely beexpanded to autoimmune diseases,

including aplastic anemia, lupus, sicklecell anemia, and lupus.

Funding for the clinical trials was providedby the National Heart, Lung and Blood Instituteand the National Cancer Institute.

GETTING BREASTCANCER DRUGS RIGHTTO THE SOURCEScience Translational Medicine

To best treat the precursors of breast can-cer, Kimmel Cancer Center investigatorsrecommend going directly to its source.Breast cancers most often arise in the cellsthat line the breast ducts, and BreastCancer Program directors SaraswatiSukumar, Ph.D., and Vered Stearns,M.D., have developed a method to deliveranticancer drugs directly to these ducts. Inthis intraductal therapy, anticancer drugsare administered via a tiny catheter insertedthrough the nipple into the breast ducts.

Sukumar developed and proved thetherapy to be effective in animal models

over the last decade and now Stearns hasdemonstrated in a small study of 17 patientsthat it can be done safely in humans. “Thishas been classic translational medicine collaboration between a bench researcherand a clinician scientist,” says Sukumar,Barbara B. Rubenstein Professor of Oncology.

The intraductal delivery resulted in a higher concentration of anticancerdrugs in the breast than in the blood-stream, while typical intravenouschemotherapy provided relatively highconcentrations of drugs in the bloodbut very little, if any, in the breast, saysStearns, the Breast Cancer Research Chairin Oncology. “Our results support thetheory that by treating the breast tissuedirectly we can reach a much morepotent drug concentration where it is needed and with far fewer adverseeffects on tissue outside the breast,”she says.

In her animal models, Sukumar testedintraductal delivery of four standard anti-cancer drugs. One, called 5FU, proved to

Fuchs

Saraswati Sukumar (left), and Vered Stearns


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be the most effective, both in preventingand treating cancers. More important, itappears to initiate an immune response, atleast in animal models, that suppressestumor formation in non-treated ducts.Sukumar says this is a key finding as somebreast ducts in women are not connectedto the nipple and, therefore, are not reach-able by intraductal chemotherapy.

Sukumar and Stearns are now planningstudies of intraductal 5FU therapy as a wayto prevent breast cancer in women whohave an inherited predisposition to the disease or who have precancerous breastlesions. Sukumar says, “In principle, onecould do such a procedure every ten yearsor so to keep one's breasts tumor-free, as analternative to having the breasts removed."

This research was funded by the NationalCancer Institute, Windy Hill Medical Center,the Mary Kay Ash Foundation and the SusanLove Research Foundation.

GENE TEST IDS BADPANCREATIC CYSTSScience Translational Medicine

Kimmel Cancer Center scientists havedeveloped a gene-based test to distinguish precancerous pancreaticcysts from harmless cysts. The investi-gators estimate that these fluid-filled cysts are identified in more than a millionpatients each year, and their test mayeventually help some of these patientsavoid needless surgery.

“Most cysts are benign," says pathologistRalph Hruban, M.D., director of theJohns Hopkins’ Sol Goldman PancreaticCancer Research Center, “but distinguish-ing between the harmless and dangerousones is challenging for doctors andpatients alike."

Helping to make the distinction is leading cancer genetics expert BertVogelstein, M.D.Vogelstein and teamanalyzed 132 precan-cerous cysts for mutations in 169 known cancer-

causing genes. The team found two genes(GNAS and KRAS) commonly mutatedand found correlating mutations of theGNAS gene in tumor cells of eightpatients with pancreas cancers that haddeveloped from pancreas cysts. Neithermutation was found in the benign cysts.

“There has long been a need for accu-rate, quantitative ways to identify cyststhat are more worrisome and to helppatients avoid unnecessary surgeries forharmless cysts," says Vogelstein.

Genetic analysis of the kind reportedin the new study offers a new way tosort the potential of these cysts tobecome cancerous. Further studies ona larger number of patients must be donebefore the gene-based test can be widelyoffered. Vogelstein says, however, thatthe technology for developing a gene-basedtest in this case is relatively straightforwardbecause “the mutation occurs at one spotin both of the genes."

Major funding for the study was providedby the Lustgarten Foundation, a private,nonprofit foundation dedicated to fundingpancreatic cancer research. Other fundingwas provided by the Virginia and D.K.Ludwig Fund for Cancer Research, the SolGoldman Center for Pancreatic CancerResearch, the Joseph L. Rabinowitz Fund, the Michael Rolfe Foundation, the IndianaGenomics Initiative of Indiana University,which is supported in part by LillyEndowment Inc., the J.C. MonastraFoundation, Swim Across America and the National Institutes of Health.

WATCH AND WAITAPPROACH FORPROSTATE CANCERJournal of Clinical Oncology

A Johns Hopkins study of 769 men fromacross the United States with low-gradeprostate cancer finds no harm in delayingtreatment for men 65 or older as long asthe cancer’s progression and tumorgrowth are closely monitored through“active surveillance” and there is no dra-matic worsening of the disease over time.

“This study offers the most conclu-sive evidence to date that active surveillance may be the preferredoption for the vast majority of oldermen diagnosed with a very low-gradeor small-volume form of prostate cancer,” says study leader and urologistH. Ballentine Carter, M.D. “These aremen with a favorable risk disease profileto begin with.”

The study, which ran from 1995 to 2010,is believed to be the largest and longeststudy of men initially diagnosed with theearliest stage of prostate cancer. Thesemen have cancers characterized as slow-growing and very nonaggressive and have a very small chance of dyingfrom the disease. “The vast majority ofthese men are ideal candidates for activesurveillance because they are older andare able to avoid the risks and complicationsassociated with surgery and radiationtreatments, including incontinence, impotence, and other bowel and urinaryproblems.

Some 217,000 men in the United Statesare diagnosed each year with prostatecancer, the majority of them are olderthan 65 and have a low risk of dying fromthe disease if treatment is deferred, Cartersays. Yet, more than 90 percent of thesemen with low-risk disease, includingsome 80 percent of those over 75, are likely to choose some form of treatmentinstead of surveillance. “Our findingsreally underscore the need to addressexcessive treatment of this milder stage of the disease in older men, especially seniors,” says Carter.

Current guidelines endorsed by the National Comprehensive CancerNetwork already list active surveil-lance as a preferred course of actionfor many older men, especially seniors,and could be broadened as a result ofthe study. Carter and team are workingwith the Prostate Cancer Foundation todevelop a web-based educational programon active surveillance for men newly diag-nosed with the disease.

The study was funded by the ProstateCancer Foundation and the Patrick C. WalshProstate Cancer Research Fund.

Vogelstein

WATCH A VIDEO

WWW.HOPKINSKIMMELCANCERCENTER.ORG92011/2012 PROMISE&PROGRESS

SAFER RADIATIONTHERAPYThe Joint Annual Meeting of the AmericanAssociation of Physicists in Medicine (AAPM)and Canadian Organization of MedicalPhysicists

Radiation therapy is an effective and safestaple of cancer treatment. However, themultistep complexity of radiation therapy,and the numerous precision measurementsits use entails, can sometimes lead to mistakes, with patients getting too littleradiation where it’s needed, or too muchwhere it isn’t.

Radiation oncology and molecular radia-tion sciences expert Eric Ford, Ph.D., andpediatric radiation oncologist StephanieTerezakis, M.D., led the first-ever safetyanalysis of radiation oncology. Workingwith researchers at Washington Universityin St. Louis, Ford and team gathered dataon about 4,000 “near miss” events thatoccurred during 2008 to 2010 at both JohnsHopkins and Washington University. Theyfocused their attention on 290 events that,had they not been caught in time, couldhave resulted in serious harm to patients.They determined that a combination ofapproximately six common qualityassurance (QA) measures, including useof hardware built into many radiothera-py-delivery machines and a relativelysimple checklist, would have preventedmore than 90 percent of the potentialincidents. The checklist includes reviewsof patient charts before treatment by both

physicians and radiation-physicists whocalculate the right dose of radiation and amandatory “timeout” by the radiation ther-apist before radiation is turned on to dou-ble-check that the written treatment planand doses match what’s on the radiationdelivery machines. “While clinicians in thisfield may be familiar with these qualityassurance procedures, they may not haveappreciated how effective they are in combination,” says Ford

By contrast, a common QA measureknown as pretreatment IMRT (intensitymodulated radiation therapy), was foundnot to be useful. In this measure, staff performs a “test run” of the radiotherapydevice at its programmed strength with nopatient present. “This is important to know,because pre-treatment IMRT often consumesa lot of staff time,” he says.

In a follow up study surveying radiationtherapy specialists, Ford and team identifiedfear of getting colleagues in trouble, liabilityissues, and embarrassment as the mostcommon explanations given for not report-ing errors. He and Terezakis are membersof the AAPM Working Group on thePrevention of Errors, which is developing away to have treatment errors and near-missesreported and sent to a central group forevaluation and dissemination to clinics,says Ford. “It could work in ways similarto how air and train accidents are reportedto the National Transportation SafetyBoard,” he noted.

The study was funded with a pilot researchgrant from Elekta Inc.

TO DETECT COLON CANCER,LOOK IN THE MOUTHFamilial Cancer, June 2011Oddly enough, looking inside the mouthmay be the best way to detect a hereditaryform of colon cancer. According toresearchers, people who have a hereditarycolon cancer syndrome known as familialadenomatous polyposis (FAP) also haveabnormally dense blood vessel growth inthe lining of their mouths.

“A higher blood vessel density in themouth may reflect an abnormal state ofcells lining the digestive tract, includingthe oral cavity, that predisposes people to colorectal cancer and precancerouspolyps,” says Francis M. Giardiello,M.D., director of the Johns HopkinsHereditary Colorectal Cancer Program.

FAP, an inherited genetic disease thatcauses hundreds of precancerous polypsto form in the colon, some of which eventually develop into colon cancer, iscurrently diagnosed with costly DNA testsand colonoscopies, and sometimes still goesundetected until colon cancer develops. As a result of this work, Giardiello andteam developed a simple and quickscreening test. Working with collabora-tors at the Catholic University ofAmerica, researchers developed anautomated camera-like device thatmeasures the vascular density in thelining of the mouth.

The investigators tested their device,scanning the lower lip of 33 patientsenrolled in the Johns Hopkins ColorectalCancer Registry as well as 50 people withno personal or family history of colorectalcancer. Measurements were significantlyhigher among FAP patients when comparedto healthy controls.

Measurements were also high when the test was performed on five of Giardiello’spatients who have multiple polyps but noknown underlying genetic cause. “Theseresults suggest that the high vascular density may be an alternative marker forcolon cancer risk, even when we can’t findthe gene mutation causing it.”

The research was funded by the John G.Rangos Sr. Charitable Foundation and theClayton Fund.

Eric Ford and Stephanie Terezakis


JOHNS HOPKINS PHYSICIANS,

SCIENTISTS, AND ENGINEERS

WORKING TOGETHER TO

FIGHT CANCER

EngineeringCures

by Valerie Matthews MehlP H O T O B Y K E I T H W E L L E R


Dan Stoianovici andteam have developed arevolving needle thatworks like a drill,rotating as it entersan organ, creatingless force against thetissue, and therefore,providing more preciseplacement. See hisstory on page 25.

[ C O V E R S T O R Y ]

ADD ENGINEERS TO THE LIST OF SPECIALISTSENGAGED IN THE FIGHT AGAINST CANCER.It is not unexpected. Johns Hopkins is revered for its braintrust and the willingness and desire of its leadership toapply knowledge to improve the health and wellbeing of humans. Johns Hopkins, after all, was the site of the first department of biomedical engineering—the very first organized effort that applied the tools of engineering tohuman medicine. It is a brilliantly simple concept. Gathertogether the smartest people, give them the freedom to pursuenovel approaches, and good ideas will almost alwaysresult. This is perhaps the cornerstone of Johns Hopkins’pioneering success in so many fields. With world-classprograms in engineering and medicine and some of the mosttalented scientists in both fields, why not bring them together.

“MORE INTERACTION stimulates creative ideas,” says Kimmel CancerCenter Director William Nelson. “It leadsto connecting two things together that havenever been connected before. With more of this happening it is almost certain thatsomething innovative will come about.”

The Cancer Center at Johns Hopkinswas built on the premise of collaboration.The urgency of the problem demanded no less. Laboratories were located directlyoff the patient wings to ensure the quick

transfer of discoveries from scientists toclinicians. Nowhere at Johns Hopkinswas the physician-scientist, those whowork both at the bench and the bedside,more visible than in the Cancer Center.Kimmel Cancer Center investigators andclinicians were doing “translational” medicine-transferring basic science discoveries to cancer medicine-longbefore there was a word for it.

Therefore, it is not surprising that anew and different type of collaboration

has emerged. This way of working, onecould say, is in ourmetaphorical “genes.”

Pioneering discover-ies in genetics and epigenetics by JohnsHopkins KimmelCancer Center investi-gators have revealedthe very origins of cancer and uncovered

new targets for treatment and drugs thathit these targets. Engineers bring tech-nologies that allow researchers to pick thebest target, deliver drugs effectively to thetarget, and monitor whether or not it getsthe job done. Cancer researchers madepersonalized cancer medicine possible.Engineers made it doable.

“We have to ask ourselves, ‘Why isJohns Hopkins so successful?’” says Dean of the Whiting School of EngineeringNicholas Jones. “The collaborationsbetween investigators in the trenches all the way up through the Deans andDirectors of departments surely musthave something to do with it.”

Collaborations between oncologistsand engineers are certainly not new to the Kimmel Cancer Center. Diseases likecancer demand forward-thinking study,and our investigators have always lookedto innovation to develop new methods tocontrol and cure cancer. Engineers andphysicists, including John Wong, Justin

ENGINEERING CURES WORKING TOGETHER TO F IGHT CANCER


C

Hanes, and Martin Pomper work in thecancer center with the sole purpose ofusing their skills to aid oncologists in diag-nosing and treating cancer. Surgeons likeMichael Choti have solicited the expertiseof engineers for more than a decade tobring added precision through imageguidance and robotics tocancer surgery.

Every instrument usedand the process by whichthey operate were devel-oped by engineers.

Under the leadership ofJones, the Whiting Schoolof Engineering has infusedconsiderable resourcesinto the department toaccommodate the growthin clinically relevant programs, such asnanotechnology, computer science, androbotics. In recent years, he has added anew engineering building and a computa-tional and robotics facility. New programs,including the Engineering in OncologyCenter, Institute for Nanobiotechnology,the Center for Cancer NanotechnologyExcellence, The Center for Nanomedicine,and Physical Science Oncology Center fundand foster research projects between KimmelCancer Center scientists and engineers.

The strength of these collaborationsand their potential to improve healthcarehas not gone unnoticed. If investmentsare a measure of our success, then theKimmel Cancer Center and WhitingSchool have earned high marks. Bothhave recently received separate $30 milliongifts. These funds will help support personalized approaches to treating cancer, stemming from Johns Hopkinsresearch that distinguishes unique geneticand epigenetic differences among individ-ual patients’ cancers, explaining, at leastin part, why traditionally developeddrugs help some people and not others.

The Kimmel Cancer Center received its gift, a grant from the CommonwealthFoundation for Cancer Research, to create a Center for Personalized Cancer Medicine.It supports collaborations and researchthat accelerate the pace of developing targeted therapies based on the distinctivecellular fingerprint of each individualpatient’s cancer. The Whiting School ofEngineering grant comes from JohnsHopkins alumnus John C. Malone and

will be used to foster interdisciplinaryresearch efforts where researchers willcollaborate with colleagues from otherHopkins divisions to learn to tailor therapies for individual patients and devise systems-based approaches to medical problems, with an initial

emphasis on cancer. “This is a watershed

moment,” says Nelson,M.D., Ph.D. “There aremany opportunities forengineers and physiciansto make cancer medicinebetter. Across a whole spectrum of components-molecular genetics, epigenetics, imaging, diagnostics, and treatment-

we are doing pioneering work in engineer-ing and in medicine. Hopkins is probablybetter positioned than anyone to make revolutionary advances in human diseases,like cancer, that could only be imagined adecade ago. It’s just a question of how webring it all together.”

GENETICS, EPIGENETICS, AND PHYSICS Cancer is a genetic disease. That wasproven by researcher Bert Vogelstein andteam who first illustrated it in colon can-cer, laying out an accumulation of geneticerrors over time that cause cancer to ariseand grow. Since that pioneering work inthe 1980s, the same team has mapped thegenetic blueprint of nearly 100 cancers.Other errors, called epigenetic events, thatalter the DNA without mutating it werealso proven by Kimmel Cancer Centerresearchers to contribute to the originationand progression of cancer. Now withcollaborations through the Engineering

department’s Physical Science OncologyCenter, Johns Hopkins teams are deci-phering a third contributor called physi-cal oncology. It is focused on solving themystery of how cancer cells break awayfrom the original tumor and form newtumors in other parts of the body. Thislittle understood process is called cancermetastasis, and it is at the heart of whatmakes the disease so deadly. Cancersthat spread are cancers that kill.

“Every tumor has mutations. But now, we are also looking at its structuraldifferences,” says Kimmel Cancer Centerinvestigator and pancreas cancer expertAnirban Maitra. “What are the physicalconsequences of the genetic and epigeneticevents on the cell? How does it change the cell structurally so that it can becomemetastatic?” asks Maitra. Epigeneticsexpert Stephen Baylin agrees. “We know that cancer cells have the ability to reprogram to respond to and see cues in their environment,” says Baylin.“Understanding what these cues are would be very helpful.”

Maitra says genetic events happen firstin cancers, but it’s what happens after-wards that scientists must begin to take alook at to get the full picture. We need onlylook to lower life forms like worms andplants to know there is more. “Worms haveas many protein encoding genes ashumans, yet humans are more evolved.There are layers of regulation and cellularcharacteristics beyond coding genes that wedon’t yet fully understand and some ofthem likely sustain cancer” he says.

Maitra has teamed up with Denis Wirtz,a chemical and biomolecular engineer anddirector of the Physical Sciences OncologyCenter to help unravel some of these

THERE ARE MANY OPPORTUNIT IES FOR ENGINEERS AND PHYSICIANS TO MAKE CANCER MEDICINE BETTER. ACROSS AWHOLE SPECTRUM OF COMPONENTS—MOLECULAR GENETICS, EPIGENETICS, IMAGING,DIAGNOSTICS, AND TREATMENT—WE AREDOING PIONEERING WORK IN ENGINEERINGAND IN MEDICINE.

Jones

(continued on page 14)


mysteries. “If we all take pieces of the puzzle, we can figure this out,” says Maitra.“Johns Hopkins is ahead of the game herebecause we do not work in isolation.Multidisciplinary collaborations aimed atmoving research discoveries to patient careare the Hopkins model. Human tissue andclinical research are revered and encour-aged here. We recognize that engineers are doing vibrant research that is directlyrelevant to our work, so it only makessense that we engage in collaborations.”

Wirtz developed a technology that, inminutes, can take thousands of distinctstructural measurements on tens of thou-sands of individual cells. It’s not easy for acancer cell to metastasize. “It’s like a steeplechase. The cancer cell has many obstaclesto overcome,” says Wirtz. It must breakaway from the original tumor and the organfrom which it arose, squeeze into narrowcapillaries, make it through the sheer forceof the bloodstream, and set up residence ina new and foreign environment.

Maitra and Wirtz are working to uncoverthe physical changes to a cell that help driveit away from its home and, against all odds,allow it to survive and thrive in a new andforeign place. Most cancers can be cured ifthey are detected and treated before theyhave begun to spread. If researchers canfigure out how metastasis occurs, theycould develop ways to prevent the deadliestevent in cancer progression.

Wirtz likens a cancer cell that metasta-sizes to a decathlon athlete. A decathloncompetition, whose winner is consideredthe world’s greatest athlete, features competitors who have physical attributes

ENGINEERING AS APPLIED TO CANCER MEDICINEDenis Wirtz refers to Kimmel CancerCenter Deputy Director Stephen Baylinas Mr. Epigenetics. The title was bestowed for Baylin’s work in linking biochemicalalterations in the DNA environment tothe initiation and growth of cancer. Thesenon-mutational alterations are categorizedas epi–in addition to–genetic. The work of Baylin and his colleagues, clinician-scientists James Herman and MalcolmBrock, resulted in some of the first uses of epigenetic abnormalities as cancer biomarkers for diagnosis and to predicthow a cancer would respond to treatment.Now Center for Cancer NanotechnologyExcellence engineer Jeff Wang is helpingmove these trailblazing therapeutic discov-eries forward more rapidly.

In 2008, lung cancer research by Brock,Herman, and Baylin found epigenetic alterations to any or all of four genes causedcancers to be more aggressive. Dependingupon the combination of altered genes, the recurrence rates of the lung cancers


The work of Stephen Baylin (center) and hiscolleagues, clinician-scientists James Herman(right) and Malcolm Brock (left), resulted in some of the first uses of epigeneticabnormalities as cancer biomarkers for diagnosis and to predict how a cancer would respond to treatment.

that make them stronger, faster, and simplymore adept than other athletes. “Millions of cells are shed by tumors every day, butonly one or two of them will have what ittakes to become metastatic. These are thedecathlon cells. We need to figure out whatthe physical properties are that give thesecells an edge,” says Wirtz.

Maitra and Wirtz are now using his cellular measurement tool in the laboratoryon human cancer cells to identify specificcellular characteristics that may determinehow aggressive a cancer will be and how it will respond to treatment. Monitoringand measuring how cells change will allow scientists to predict which ones are likely to become the lethal, metastatic type.

“This kind of technology allows us tofurther personalize cancer medicine,” saysMaitra. Within the next few years Wirtzand Maitra hope to move the technologyinto clinical use to help select drugs thatwill work best against a cancer based onthe genetic, epigenetic, and physical char-

acteristics of tumor cells. “The engineershave the coolest tools around, and they are looking to us for the right biological uses,”says Maitra. “Now, we can use this newtool to correlate gene abnormalities withparticular cellular characteristics and drugsensitivity so that we can get the most effective treatments to each patient.”

Anirban Maitra (left)and Denis Wirtz


S

WATCH A VIDEO

WWW.HOPKINSKIMMELCANCERCENTER.ORGIMAGINE THE POSSIBILITIES

BLOOD CELLS BECOME BEATING HEART CELLS

With one look through the microscope, these cells

are immediately and unquestionably identifiable.

Though silent in this microscopic form, the rhythmic

and continuing up and down motion causes the

mind to think it hears the iconic thump thump—thump thump—thump thump of a beating heart.

What appears beneath the lens of the microscope

are single heart cells, no bigger than the tip of a

needle, but as they beat, they are like tiny micro-

cosms of the life-sustaining organ.

STILL, MORE AMAZING than the cells themselves is the storyof their origin. Days earlier they were human blood cells, likethose that course through our veins and arteries, until researchersElias Zambidis and Paul Burridge altered their destiny andtransformed them into living, functioning heart cells. Now,instead of cells that are pumped out by the heart, they are part of the heart.

In a collaboration between the Kimmel Cancer Center, Institutefor Cell Engineering, and Department of Biomedical Engineering,Zambidis, Burridge, and team successfully turned blood stemcells into functional, beating heart cells.

Their methodical two-year study resulted in a simple,straight-forward recipe for changing blood stem cells into heartcells, and called upon the expertise of basic scientists, stem cellengineers, and biomedical engineers. What they accomplishedwas previously considered impossible by international leaders inthe field of regenerative medicine, and provided more evidence ofthe ingenuity, collaboration, and the relentless pursuit of answersthat allow Johns Hopkins scientists to do what others cannot.

“Many scientists previously thought that a nonviral methodlike the one we used to induce blood cells to turn into highlyfunctioning cardiac cells was not within reach, but we found away to do it very efficiently,” says Zambidis.

For Zambidis, whose research interests are in pediatric oncol-ogy and cancers of the blood, the special “plasticity” of the bloodstem cell that allows them to be transformed to a heart cell, holdsimportant clues about how leukemia and other blood diseasesdevelop and how they can be controlled. Burridge, who plans tospecialize in cardiology, will focus his continued research onrefining the technique in hope that, one day, a patient’s bloodcells can be directly turned into heart cells to therapeuticallyrepair hearts damaged by heart attack and other diseases.

To take cells from one source, in this case, blood, and transformthem into a heart or other cell type, scientists typically use virusesto deliver genes that will cause the cells to revert back to stemcells with open-slate potential to give rise to virtually any type of

cell. Viruses, however, can mutate genes and initiate cancers innewly transformed cells. As a result, Zambidis, a cancerresearcher, chose to use plasmids, rings of DNA that replicatebriefly inside cells and eventually degrade, to deliver the genes.

To cause the actual transformation from one cell type toanother, newly-reverted stem cells are placed in a controlled envi-ronment and bathed in a broth of growth factors and nutrients.The recipe for this “broth” varies from lab to lab and cell line tocell line, but Zambidis, Burridge and team created a universalrecipe that, in their studies, worked consistently on nearly adozen cell lines, and worked as well in transforming adult stemcells as it did in embryonic stem cells. To augment the cell transformation, the researchers created an oxygen-deprived environment that mimicked the natural human environment ofthese primitive cells.

Once transformed, the team set out to validate that the cellsdidn’t just look like heart cells but functioned like them as well. Forthis, they solicited the expertise of bioengineers, who developedand applied a miniversion of an electrocardiograph to the cells andproved that the cells were behaving like a normal human heart.

The discovery was only possible because Burridge was willingto do what scientists before him were not—his homework. Fortwo years, he undertook the admittedly tedious job of combingthrough dozens of journal articles citing the varied techniquesused to create cardiac cells. Next he made charts to analyze thewide range of techniques. Finally, after testing more than 100combinations, Burridge was able to narrow the choices down tofour to nine essential ingredients for each stage of cardiac devel-opment. “We took the recipe for this process from a complexminestrone to a simple miso soup,” says Zambidis.

He cautions that the cells are not ready for human testing, butsays the team continues to develop their methods, most recentlyturning blood cells into retinal, neural, and vascular cells. He is eagerfor other scientists to test the method in their own laboratories. •

Watch a video of the beating heart cells at www.hopkinskimmelcancercenter.org


N



studied increased two to 25-fold. Based onthese findings, clinician-scientists RosJuergens, Charles Rudin, and Brock initiated a clinical study of epigenetic therapy for patients with advanced andheavily treated lung cancer, and a smallpercentage of patients experienced veryrobust and long-lasting responses.

With funding from Stand Up to Cancer(SU2C), Rudin, Brock and team are hopingto develop these findings into a personal-ized treatment approach for lung cancer,and Wang’s work in developing a nano-based assay to test for alterations in theseand other genes is central to that.

SU2C support allowed the researchersto do an unusual thing-to go back and findout what happened to the patients theythought they didn’t help. They reviewedthe records of patients who were partici-pating in a clinical trial of epigenetic therapy because their lung cancers had not responded to standard therapy.Specifically, Rudin, Brock and team wereinterested in some 40 patients who weretaken off of the epigenetic treatment trialbecause their tumors continued to grow.What they found surprised them all.Although many patients seemed toprogress while on therapy, many, includingthose who had received just two or threetreatments, had unprecedented and long-lasting responses. The team poured over

every scan and every clinical report, andeven re-biopsied some tumors, and couldcome up with only two explanations.Either the epigenetic therapy sensitizedtheir cancers to subsequent treatment withstandard drugs, or their improvement wasa direct response to the targeted therapy.

Targeted therapies do not work like theold cytotoxic chemotherapies, which do notdiscriminate between cancer cells and normal cells. Instead they specifically seekout and reprogram the malfunctioningmechanism within cancer cells that is caus-ing the tumors. As a result, Baylin says,targeted therapies shrink tumors moreslowly over time as they make their repairsand genes are returned to normal function.

Jerry Morton, a 61-year-old retired firefighter, was building a sandbox for hisgrandson two years ago when he learnedhe had small cell lung cancer. The cancerhad already spread throughout his lungsand to his liver. “I didn’t expect to live longenough to complete it,” says Morton.“Today, that sandbox is finished.” Morton’stumors melted away on the epigenetic treat-ment. When he recently developed a new,small tumor of the same type Rudin, Brock,and team again tried epigenetic therapy,and Morton, once again, appears to be benefitting. “The team has evidence thatthe status of epigenetic alterations in thesefour genes, assayed in the blood by sensitive

technologies that Dr. Wang is working toperfect, can predict the good responses inpatients like Mr. Morton,” says Baylin. “It is a perfect illustration of the value ofcollaborative research and translational,personalized cancer medicine.”

With such promising results, Baylinand team are now planning another trialfor newly diagnosed patients. If findingscontinue to show that the epigenetic-targeted therapy works, Wang figuresprominently in the wide clinical applica-tion. What Brock, Herman, and Baylin doin their basic science laboratory to screenfor the epigenetic alterations would be difficult to routinely do in a clinical lab, so they asked for help from engineers.Wang, who works in the Institute forNanobiotechnology, is using nanotechnology,engineering at a molecular level, to developa broad-based test that could be used routinely in any clinical laboratory to pre-dict which patients would benefit from thetargeted therapy. “This facet is criticallyimportant in taking these therapies beyondour own walls. Without the nano-techapproach, testing for the alterations mightbe too cumbersome for a clinical lab,” saysBaylin. If ongoing trials confirm the earlierfindings, Wang’s test can help ensure thatthe Johns Hopkins-based discovery becomesavailable to lung cancer patients everywhere.

ENGINEERING MOLECULESNanotechnology, in essence, refers to the field of engineering that focuses onultra-tiny functional devices and structuresthat are so minute they cannot be seen bythe human eye. Think of it as engineeringat the molecular level. Like their scientistcounterparts in molecular genetics, engi-neers who specialize in nanotechnologywork in the realm of invisibility and hadto develop new technologies just to performtheir craft.

Where nanotechnology intersects withmedicine is the focus of the Johns HopkinsInstitute for Nanobiotechnology. It beganin 2006, bringing together scientists and students from engineering, physics,chemistry, biology, medicine, and publichealth to apply the technology to the treat-

Jerry Morton, a 61-year-old retiredfirefighter, diagnosed with smallcell lung cancer, has benefitedfrom epigenetic treatments.


ment of diseases. It was the brainchildof Peter Searson and Denis Wirtz, bothengineers, whose work was centered on

the physical sciences.They began to wonderwhat Johns Hopkinsengineers and physi-cists could contribute ifthey collaborated withmedical scientists and

directed their research towards healthcare and medicine. Research teams com-prise both engineers and medical researchscientists, a point Searson says cannot beoverstated. “The engineers attend labmeetings and visit the clinic and workdirectly with clinicians so that we under-stand the problems clinicians are facing,”says Searson. The model has been quitesuccessful, earning the Institute two largeNIH center grants; one for the PhysicalScience Oncology Center and another forthe Center for Cancer NanotechnologyExcellence (CCNE).

“Physicians and engineers approachproblem solving in different ways,” sayscancer immunology expert Hy Levitsky,who trained in bioengineering beforegoing into medicine and is now workingwith engineers to improve cancer vac-cines. “As an oncologist, I can point to aproblem, but I don’t have the expertise toknow the spectrum of possible solutions.Engineers can look at the problem from a very different perspective. When webring the two perspectives together, wearrive at unique approaches we may nothave otherwise found.”

A TROJAN HORSE FOR THE CANCER WARJustin Hanes, a chemical and biomedicalengineer specializing in nanotechnologyfor cancer treatment, explains that ananoparticle is to a soccer ball what a

soccer ball is to theplanet earth. Suffice it to say that we’re talking very small.

As small as they are,part of their value incancer medicine is

that they are bigger than other things.Nanoparticles are much larger than smallmolecules—agents commonly used totreat cancer. Hanes says hundreds ofthousands of small molecules can fit intoone nanoparticle. As a result, they can beloaded up like a Trojan horse and sent outto deliver their cargo to tumors.

Hanes is a member of the CCNE whichhas the specific aim of using nanotechnologyto improve the treatment of cancer. He is excited about the prospects of nan-otechnology to improve the delivery ofanticancer drugs and combat toxicities.“Right now, we use systemic cancer therapies, which are incredibly useful, buttypically a very small percentage of thechemotherapy ends up in the tumor. Therest of it poisons normal cells throughout

the body,” explainsHanes. He uses nanotechnology in anattempt to reverse thatratio so that anticancerdrugs go directly totumors with very little

injury to normal cells. “Think of a tumoras a weed in a prized rose garden. Whatwe do now is spray the entire rose gardenwith weed killer,” says Hanes. “But, wecan only spray so much poison or we riskkilling the roses.” The project he is workingon with lung cancer experts CharlesRudin and Craig Peacock is a nano-basedtreatment that seeks out and targets cancercells. “Like a pre-addressed envelope, weare developing methods to direct them to

where we want them to go,” says Hanes.Hanes directs the Center for Nano-

medicine where he and his colleagues arecurrently working on anticancer-drug-fillednanoparticles that can be inhaled into thelung. His team created the first nanoparticlesystem that can penetrate the mucus liningthe lung airways. In the past, inhaled forms

of nano-therapy have failed largely becausethe lungs’ natural mucus barrier, in placeto keep out bacteria and other infectiousinvaders, swept the drugs away beforethey could go to work. When Hanes andteam discovered that the mucus lining was more like a net than a blanket, theyconstructed nanoparticles small enoughand slippery enough to get through theholes in the sticky mucus “net.”

Hanes’ particles are composed of twoparts made of molecules routinely used inexisting medications. An inner core trapstherapeutic agents inside while a denseouter coating allows a particle to slipthrough mucus nearly as easily as if it were moving through water. Thenanoparticles cause no immune or inflammatory response so drugs travelfreely through the lungs, including areasscientists believed were impenetrable,releasing their anticancer cargo over anextended period of time.

Hanes’ nano-based approached could beapplied to cancers of any mucus-lined organ,including the colon and cervix. He saidsuch treatments could be ready for clinicaltrials in as little as five years and cost aboutthe same as traditional chemotherapy.

AS AN ONCOLOGIST, I CAN POINT TO A PROBLEM, BUT I DON’T HAVE THE EXPERTISETO KNOW THE SPECTRUM OF POSSIBLESOLUTIONS. ENGINEERS CAN LOOK AT THE PROBLEM FROM A VERY DIFFERENTPERSPECTIVE. WHEN WE BRING THE TWOPERSPECTIVES TOGETHER, WE ARRIVE ATUNIQUE APPROACHES WE MAY NOT HAVEOTHERWISE FOUND.

Searson

Hanes

Peacock


CFROM THE FAMILY ROOM TO THE OPERATING ROOM

SURGEON FINDS NEW USES FOR VIDEO GAME SYSTEMS LIVER CANCER SURGEON Michael Choti is moving gamingsystems from the family room to the operating room. In collabo-ration with experts from engineering, Choti and team are applying the image-guided technology used in interactive gaming systems like the Nintendo Wii® and Microsoft Kinect®systems to medicine.

These newer iterations of video games use cameras, motionsensors, tracking systems and accelerometers to allow players to interact directly with the game. Choti, EmadBoctor, a radiology and computer science engineer,and Philipp Stolka, a post-doctoral engineering fellow, are working to apply the same technology to create image guidance and tracking devices foruse in cancer surgery and treatments. “Currentrobotic and image-guided tracking systems tend to be cumbersome and extremely expensive,” saysChoti. “Our approach makes use of sophisticatedand mobile, but relatively cheap technology, whichshould broaden its appeal.”

A Wii remote contains accelerometers and infra-redcameras that calculate relative position and orienta-tion and beam the information continuously to thegame controller via a “Bluetooth” radio link. A computer receivesand processes the Bluetooth signals. In one adaptation, Choti and team used the Wii remote to transform standard ultrasoundimaging into a more readable 3-D imaging. Although 3-D ultra-sound probes exist, Choti says they are unwieldy and expensive.

However, with the position and orientation information from the Wii remote and local optical sensors, a computer couldstraightforwardly turn the 2-D ultrasound image into a more readable and useful 3-D ultrasound image. “Our setup, in principlewould, allow clinicians to convert a 2-D ultrasound probe into a3-D probe that’s portable and easy to use in a variety of applications,”says Choti.

In another application, Choti and his engineering team showedthat Kinect, the optical hardware from Microsoft,Inc., and image-recognition algorithms used toidentify and track the location and orientation ofobjects in its visual field, could be adapted tolocate and track the motions of a biopsy needle.

One of the next steps in the development ofthese systems will be to combine the tracking of animaging device such as an ultrasound probe with thetracking and 3-D guidance of a surgical instrumentsuch as a needle, says Choti. “That combinationwould give us a relatively inexpensive and portablesystem for image-guided surgical procedures,” hesays. Microsoft executives have expressed interestin working with Choti and team to develop the

technology specifically for medical applications.“This shows the value of looking at other fields, whether it is

engineering, geology, or computerized gaming,” says Choti.“Collaborations—and Hopkins is good at collaboration—can leadto unexpected uses of technology that are of value to patients.”•



Left to right,Philipp Stolka,Michael Choti, and Emad Boctor

ON TARGET

MOLECULAR IMAGINGCentral to targeted therapies is the abilityto verify that an agent is hitting its intendedtarget and having an impact against thecancer. Targeted agents work by killingcancer cells outright or, in some cases, by

reprogramming brokenmechanisms within theDNA to kill cancer cellsmore slowly over time.Traditional radiology,like CT, is focused onanatomy and explores

the structure of organs and tumors andprimarily measures reduction or growthin the size of tumor over a period ofmonths. These types of scans cannot seeor measure what is going on within theDNA of cancer cells.

This shortfall has led to the field ofcancer molecular imaging and theresearch of forward-thinking scientistslike Martin Pomper, a radiology expertwho came to Johns Hopkins in the early1990s because it was one of the few insti-tutions where molecular imaging researchwas being done. Pomper has collaboratedwith chemical and biomolecular engineersand other scientists to adapt radiology tothe molecular level.

Over the last two decades with advancesin genetics and epigenetics leading to newtherapies aimed at interfering with thesecancer-causing alterations to the DNA,cancer imaging has grown from a devel-oping program of the Kimmel CancerCenter to a formal program vital to itsability to move these new treatments fromtest tubes to patients.

Pomper says molecular radiology hasthe ability to image inside the cell andreveal to clinicians when a cancer cell ispoised to metastasize, permitting a thera-peutic strike before the cancer makes thiscritical and often deadly transformation.

More recently, Pomper has been developing agents that make cancer cellsfluoresce so that they can be tracked andmonitored—tracked so that scientistsknow where new targeted agents aregoing, and monitored so they know if theagents are having any benefit. “This helpsus to see quickly if drugs are hitting theirtargets and doing what we expected themto,” says Pomper. “We can then personal-ize treatments to individual patients. Wecan give one dose of a drug. If cells lightup, we know we have the right drug. Ifnot, we know to move on to somethingnew, rather than waiting three months fora scan to show that the tumor has grown.”Currently, this type of molecular imagingis done primarily in research studies andin conjunction with pathology and scansto validate its capabilities. Once proven,however, Pomper says, it has the potentialto complement, if not replace, CTs andsome types of pathology obtained in biopsy as the primary method for detectingand monitoring cancers.

QUANTUM DOTSLight-emitting nanoparticles known asquantum dots are another molecularimaging technique Pomper is exploringwith Institute for Nanobiotechnologydirector Peter Searson. These cancer-specific quantum dots are what investiga-tors call theranostics (therapeutic anddiagnostic) for their ability to aid both in

the detection and treatment of cancer.Pomper says they can be engineeredusing a special coating that makes themseek out and bind only to cancer cells, andthey can also be loaded with drugs tocarry to tumors. In collaboration withSearson and Anirban Maitra, Pomper isattaching targeting molecules to quantumdots that are attracted to proteins over-expressed in pancreas cancer and workingon methods to make the quantum dotscirculate throughout the bloodstream totarget tumor cells. “These would be likeradioactive warheads that can travelthroughout the body and not cause anydamage until they come into contact witha cancer cell,” he says.

IMAGING IN CANCER VACCINESIn another example of targeting and monitoring treatments, cancer immunologyexpert Hy Levitsky is working with

engineer Jeff Bulteto improve cancer vaccines. Bulte, a radiologist and biomedical, chemical,and biomolecular engineer, has devised

a way for Levitsky to monitor and trackthe activity of immune-boosting cells inresponse to cancer vaccines.

Several key biological events must occurafter injection with a cancer vaccine to getthe immune system to kill cancer cells.Levitsky says the antigens contained inthe vaccine must move from the injectionsite into the lymph nodes, where immunityis initiated. Cells, called antigen-presentingcells, have the pivotal job of capturing the antigens and delivering them to thelymph nodes. This critical step of antigentransport is often the place where vaccinetherapy breaks down. “If we don’t getthis step to happen efficiently, there is nohope that the vaccine will work,” saysLevitsky. As a result, clinicians almostalways use adjuvants—additional treat-ments given in conjunction with cancervaccines to help antigen-presenting cellsmake the journey to the lymph nodes.

WE CAN GIVE ONE DOSE OF A DRUG. IFCELLS LIGHT UP, WE KNOW WE HAVE THERIGHT DRUG. IF NOT, WE KNOW TO MOVE ON TO SOMETHING NEW, RATHER THAN WAITING THREE MONTHS FOR A SCAN TOSHOW THAT THE TUMOR HAS GROWN.


Bulte


Pomper

MORE INTERACTION stimulates creative ideas,” says Kimmel CancerCenter Director William Nelson. “It leads to connecting two things togetherthat have never been connected before. With more of this happening it isalmost certain that something innovative will come about.

The Cancer Center at Johns Hopkins was built on the premise of collaboration. The urgency of the problem demanded no less. Laboratorieswere located directly off of patient wings to ensure the quick transfer ofdiscoveries from scientists to clinicians. Nowhere at Johns Hopkins wasthe physician-scientist, those who work both at the bench and the bedside,more visible than in the Cancer Center. Kimmel Cancer Center investigatorsand clinicians were doing “translational” medicine-transferring basic science discoveries to cancer medicine-long before there was a word for it. •


Bulte and Levitsky recruited M.D., Ph.D.-student Chris Long to work jointlybetween the two laboratories to devise amethod to quantify this process of antigendelivery. Long developed a technologythat uses MRI (magnetic resonance imaging) and iron nanoparticles to trackthese vaccine-transporting cells. Themagnetic iron particles become visiblewhen exposed to a strong magnetic field,such as that used in MRI. Long was the first scientist to show that antigen-presenting cells can capture iron-particlelabeled antigens and be tracked insidethe body. Before this work, cells couldonly be labeled through contrast agentsadministered outside of the body. Themethod allows Levitsky to know exactlyhow many antigen-presenting cells capture vaccine antigen and make it to thelymph nodes and also to test how wellvaccine adjuvants are improving thistransport. “Within three to five days of

vaccination, we can see if the vaccine isworking as it should,” says Levitsky.“Adjuvants are almost always given withvaccine therapy, so this technology aidsus in a critical area of cancer research.”More important, Levitsky says it could bemoved to humans quickly. “All pieces ofthis project—the adjuvants, MRI, andcontrast—have already been used safelyin humans, just not in this way,” he says.

IMAGINE GOING DOWN THE VESSEL TREE,DELIVERING A CHEMOTHERAPY-FILLED LIQUID THAT GETS DRUGS TO THE TUMORAND THEN POLYMERIZES [UNDERGOES ACHEMICAL REACTION] TO BLOCK OFF FURTHER BLOOD SUPPLY TO THE TUMOR AS YOU WATCH IT ALL UNFOLD.



Cancer immunology expert Hy Levitsky

CANCER IMAGING DEVICESScientists in the Department of BiomedicalEngineering make image-guided devicesfor diagnosis and treatment of diseases,including cancer.

Devices that produce remarkably clearand detailed images of cells are aidingoncologists, radiation oncologists, andsurgeons in the detection and treatment of cancer. Xingde Li adapted a device hedeveloped to look at the walls of bloodvessels and arteries for use in cancer. Li’s optical imaging device can be placedin a patient’s esophagus where it producessuper-high resolution images of theesophageal wall. The images are so clearclinicians are able to decipher normal cells from a benign inflammatory conditioncalled Barrett’s esophagus that can predispose those affected to developingesophageal cancer.

A similar device is in development toassist neurosurgeon Alfredo Quiñones-Hinojosa in delicate brain cancer surgery.When removing a tumor from the brain,the command center for all that is human,surgeons work diligently to protect braintissue not invaded by the tumor. Surgeonswalk a clinical tightrope—they mustremove as many tumor cells and as fewnormal cells as possible. Leave tumorcells behind and the tumor may return,but harm normal brain cells, and thepatient could lose important mental andphysical functions. Typically, surgeonswill start at the border of the tumor,painstakingly shaving off very small sections, piece by piece. Figuring outwhen they are finished can be a difficult

problem, so Li is working on a microscopic device that surgeons can place againstcells to quickly distinguish tumor cellsfrom normal cells.

Department chairman Elliot McVeighand team also are working to make lungcancer detection safer and more accurate.The quality of CT scans has improved sogreatly that it can detect tiny tumors inthe lung no larger than a few grains of rice.This type of early detection, occurringbefore a cancer produces any symptomaticevidence of its existence, could allow forearlier intervention. To intervene, partic-ularly with targeted therapies personal-ized to the specific DNA alterations in atumor, clinicians must be able to get anaccurate biopsy of the tumor. Usually thisis done through bronchoscopy, but it is notan exact method. “I’ve watched manybronchoscopies, and sometimes it can take10 to 20 attempts to get the right tumorsample,” says McVeigh. “This can be verytraumatic for the lung and the patient. Wewant to help the physician get the importantcells while causing the least amount of tissue damage.” His team has developed a

targeted system that can be used in combi-nation with CT images, the bronchoscope,and fluoroscopy to provide real-time movingimages inside the lung. It transforms thetumor into an easily visible target that makeseven tiny tumors easier to see and biopsy.

Image-guided methods for localizeddelivery of chemotherapy are anotherfocus for McVeigh. Imagine a patient inan MR (magnetic resonance) scanner, and her physician is using the images it displays to clearly see and direct a needleor catheter directly to her tumor, injectinghigh doses of anticancer drugs into andaround the tumor. In some cases, thephysicians could potentially place a needleinto a blood vessel feeding the tumor andinject an agent that would harden andstarve a tumor to death. The precise hardening agents to be used are still beingstudied. “Imagine going down the vesseltree, delivering a chemotherapy-filled liquid that gets drugs to the tumor andthen polymerizes [undergoes a chemicalreaction] to block off further blood supplyto the tumor as you watch it all unfoldunder image guidance,” says McVeigh.

Rachel Karchin (right)and student

JOHNS HOPKINS MAKES IT POSSIBLE TOFORGE COLLABORATIONS WITH PEOPLEACROSS MANY DISCIPLINES, AND THESECOLLABORATIONS ARE SPEEDING THE PACE OF DISCOVERY.



I

In essence, this method gets the cancer drugdirectly to the tumor and then blocks theexit, keeping the anticancer drugs in andthe tumor-nourishing blood supply out.

“Our clinicians are wonderful aboutembracing engineers,” says McVeigh. “One of the best things about Johns Hopkinsis that so many are hugely famous for theirwork, but you wouldn’t know it. You sit at atable and talk to them about a project, andyou go back and read about them and learnthey are ridiculously famous. People hereare great to work with. They are not protec-tive about their ideas. They share them. It’sin the culture of Johns Hopkins. It’s whowe hire.” McVeigh says he finds that scien-tists and clinicians at Johns Hopkins arefocused on the overall mission rather thantheir own, individual accomplishments. “Ican show up at any lab meeting anywherein this institution and be welcomed. This isthe perfect research environment.”

MAKING SENSE OF IT ALLIn terms of engineering, perhaps one ofthe greatest contributions to cancerresearch is in the computer engineeringand computational science that hasallowed researchers to make sense of thevolumes of data generated by genetic andepigenetic discovery. “Engineering is notonly responsible for instruments we use in sequencing the genomes of cancer butalso in helping us interpret the raw datawe get from it,” says leading cancer geneticsexpert Bert Vogelstein. “It is much likehieroglyphics went it comes out. It is computer scientists and engineers thatturn it into meaningful data.”

Their laboratories are not like those wetypically associate with medical research.Take for example the laboratory ofRachel Karchin, a computer scientist inthe department of biomedical engineering.Instead of benches, there are desks withcomputers. Just beyond the computer labis a large, dark glass-enclosed room fillednearly floor to ceiling with computers.Green lights that glow and blink as ifcommunicating in some futuristic codeare the only outward sign of the complexcalculations occurring within.

L

Karchin is working with KimmelCancer Center investigators BertVogelstein, Kenneth Kinzler, VictorVelculescu, and Nickolas Papadopoulosto help them sift through the vast geneticblueprints of cancer to identify mutationsthat warrant further study. “Our role it to try to distinguish which of thesemutations are worth investing labresources, money, and time in followingup,” says Karchin.

The mutational landscape of tumors isquite diverse, characterized by alterationsin a variety of genes which differ frompatient to patient. Karchin is helpingthem separate the wheat from the chaff,deciphering the mutations that are actually driving the cancer from thosethat are just along for the ride. A cancercell acquires thousands of different alterations, but only a few of thesechanges will lead to cancer. “We make it tractable,” says Karchin. “We offer away to prioritize large amounts of data.Karchin is well schooled in this type ofwork. She received her doctorate in com-puter science, with a focus on computa-tional biology, from University ofCalifornia, Santa Cruz, where the humangenome was assembled in 2000. She cameto Johns Hopkins University in 2006 to join its Institute for ComputationalMedicine. The opportunity to work withresearchers of the magnitude of Vogelsteindrew her here, she says. “Johns Hopkinsmakes it possible to forge collaborationswith people across many disciplines, andthese collaborations are speeding the paceof discovery,” says Karchin.

Karchin and team have helped KimmelCancer Center researchers predict whichchanges in the genetic code may cause pancreas cells to turn cancerous. Cancerresearchers sequencing the DNA from

pancreas tumors and comparing it to nor-mal tissue, found nearly 1,000 alterationsunique to the pancreas tumors where justone letter in the ATCG chemical alphabetwas changed. They turned this sequencedata over to Karchin’s team for assessment.

The researchers developed a computerprogram that listed all of the individualgenetic changes suspected of causing cancer and those highly unlikely to causecancer. It employed 70 different predictive

features for each change to distinguishcharacteristics of the so-called drivermutations—those alterations that contributedirectly to the cancer development—fromother genetic changes. They used the program to assess the 1,000 pancreas cancer associated alterations, scoringthem with numbers between zero andone, with zero indicating a likely driverand one indicating an unlikely driver.“Our results can help cancer researchersset experiments to see how importantthese changes are in pancreas cancer andwhether or not they are good targets forpotential drug treatments,” says Karchin.“Researchers may want to make a mousemodel of a mutation that could be impor-tant in cancer so that they can test aninhibitor drug. We help them figure outwhich mutation to pick.”

DECODING THE DATALike Karchin, Steven Salzberg is focusedon helping investigators interpret the billions of data points generated byhuman genome sequencing. Researcherssequencing the genomes of a variety ofhuman diseases have called upon hisexpertise. He and his team have developedcomputer software that has been usedaround the world to whittle the datadown to the few mutations that couldpotentially be targeted clinically. As Johns

Hopkins uses its genetic discoveries topersonalize medicine to the unique cellular characteristics of each individual’sdisease, scientists like Salzberg play anessential role.

Salzberg, a biologist and computer scientist, came to Johns Hopkins to focusmore intensely on human genomics. Untilnow, his work has primarily focused onbacterial, viral, animal, and plant genomes.In 2001, he was called in to help sequencethe anthrax sent through the mail in the2001 terrorist attacks, and is now part ofthe Johns Hopkins research teams helpingcancer centers make sense of complexcancer genomes. Salzberg and colleaguesidentified mutations that helped the FBItrace the anthrax to a single vial at Ft. Detrick in Frederick, Md. Cancerinvestigators are hopeful he can againhelp zero in on a killer: this time the target is genes that cause cancer.

Salzberg’s team has developed one of the first off-the-shelf programs that system-atically and accurately find fusion genes.These are, as the name implies, two piecesof different chromosomes that becomefused together in error. It turns out thatfusions rarely happen in anything but cancer so they have become a major focusin cancer research. This jumbled up DNAis not a therapeutic target, but because it is so specific to cancer, it can serve as a biomarker for early detection of tumorcells before they are visible and as a way to monitor whether a treatment is working.If cancer cells are disappearing then soshould the fusion genes.

Until recently, cancer researchers didnot appreciate the importance of thesetypes of alterations or how common theywere in cancer, says bioinformatics expertSarah Wheelan. Genetics and epigeneticsexpert Victor Velculescu came upon similargene rearrangements, almost by accident,when he was looking for gene mutationsthat could be potential therapeutic targets.Functionally, he wasn’t sure what thefused genes did but he quickly recognizedthat they were unique to cancer cells andcould be used for individualized cancerscreening and monitoring. Wheelan says

ENGINEERS ARE THE TECHNOLOGY EXPERTS,AND PHYSICIANS AND SCIENTIST ARE THE DISEASE EXPERTS. BOTH ARE NEEDED TO CONQUER DIFFICULT PROBLEMS LIKE CANCER.



can be added to, was written so that itcould be used to find any known mutationin essentially any cancer. “We are still afew years away, but it demonstrates thatwe can do this in the physician’s office,”says Salzberg. The cost—about $5,000 tosequence a genome—may be the onlymajor limiting factor, but he and other scientists say these costs are declining.

Helping Salzberg and Wheelan towardthese personalized medicine goals isAlexander Szalay, an astrophysicist andacclaimed computer science visionary.Szalay, the director of the Johns HopkinsInstitute for Data-Intensive Engineeringand Science, designed new computerarchitecture that the Space TelescopeInstitute uses to measure the three dimen-sional positioning in space of over 200million galaxies. His technology is nowbeing used to pour through huge amountsof data related to cancer DNA to draw clin-ically relevant conclusions. In fact, whileSalzberg’s office is located on the JohnsHopkins medical campus, he has his com-puter servers in Szalay’s Physics depart-

that alterations such as this can only befound by aligning the cancer genome backto the normal genome and looking for differences. “Steve’s programs do this andmay find things we have been missing,’she says.

Salzberg and colleague Mihaela Perteaalso have written a program to find mutations in the breast cancer-associatedBRCA1 and BRCA2 genes. With only rawdata from a gene sequencer, their programquickly tests a sample for any one of about70 known mutations to these genes.“We’re trying to make this easier for peopleto do,” says Salzberg. “The software isvery efficient, and it can be run on a standard desktop so that anyone withmodest computing experience can do it.”Personalized cancer medicine is only possible if clinicians can rapidly accessand interpret the individual informationon each patient’s cancer, and this work isproof-of-concept that it can be done. Whilethe initial work was done for breast cancermutations, Salzberg says his program,which contains a library of mutations that

ment computing facility on the Homewoodcampus a few miles across town.

Szalay is developing algorithms anddatabases that store genetic informationand can connect it to patient-specific can-cer problems. It has the capability to storedata on 14,000 individual patient genomesper year and tie them securely to patientrecords. His algorithms allow researchersto do in real time what would take a basicscience laboratory a year to accomplish.Szalay’s technology allows them to quicklyquery information on large groups of cancer patients and find out what theyhave in common. For example, they could find similarities among patientswho were treated for a particular cancerand relapsed. “These pieces are essentialto being able to assess genetic informationon tumors better and faster, and they arenecessary to providing personalized therapies,” says Wheelan.

Salzberg is hoping to collaborate withGary Rosner, the Kimmel Cancer Center’s


THE FIRST THINGS one notices, upon entering the laboratory ofDan Stoianovici is the specialized machineryand tools. Is it a workshop or a laboratory? Thelarge factory-style machinery, red Craftsmantoolboxes, wrenches and other tools hangingon the wall belie the room’s true purpose. Theanatomical models seen near robotic armsand other futuristic devices offer clues.

In fact, it is both workshop and medicallaboratory. Stoianovici, Director of the Johns Hopkins UrologyRobotics Program and Laboratory tucked away on the Bayviewcampus, develops and builds, piece by piece, surgical and image-guided robotics systems used to treat urological cancers.

The plastic dummies stand in for humans as he and his teamtest their inventions–surgical systems that they build from scratch(thus the machinery and tools)–specifically to meet the uniquechallenges of prostate and kidney cancer treatment delivery.

It is a laboratory like none other where manufacturing meetsmedical research. Three industry-grade manufacturing machines,almost never seen in research laboratories, allow the researchers todesign, build, and test these highly advanced devices. Among their

ROBOTS AND OTHER MECHANICAL DEVICES

TECHNOLOGY IMPROVES PROSTATE CANCER TREATMENTprojects is an MRI-guided robot powered by pneumatics that iscompletely metal-free to be compatible with the strong magneticfield generated by the MRI. It will soon be used by urologistMohamad Allaf and radiologist Kasia Macura to target prostatebiopsies under MRI guidance. It will also be used by radiationoncologist Danny Song to perform brachytherapy, a procedure inwhich radioactive seeds are injected into prostate tumors to killcancer cells. MRI provides a much more detailed image of the prostatethan other scans and possibly allows clinicians to directly targetcancers for biopsy and treatment delivery. “I can see the prostateon the MRI screen, point to a place where I want a seed, and arobotic-driven needle puts the seed in the exact spot,” says Song.

Other technology developed in the lab focuses on needle handlings. Needle interventions are common across most medicalspecialties, and they include needles that are guided by medicalimagers, such as X-ray or ultrasound. The force as the needle ispushed into its target can move tissue, decreasing its targetingprecision. To solve this problem, Stoianovici and team havedeveloped a revolving needle driver that works like a drill, rotating as it enters, creating less force against the tissue, keepingstraighter, and therefore, providing more precise placement. •



computers intrinsic to all aspects of thecomplex planning and treatment, seemeda natural place to start.

Wong wanted to develop a systemthat would store data from clinical trialsin a way that the information did not justhelp measure the usefulness of potentialnew therapies being studied, but couldalso be queried at any time in the future toimprove the care of all patients. Theylooked to the data archive of Alexander

Szalay as the model. The system Szalayand team created not only stored data butwas also able to perform interactive, on-the-fly analyses. Wong, fellow RadiationOncology physicist Todd McNutt, andTaylor envisioned a similar system thatcould be applied to radiation therapy.

“When we participate in a multicenterclinical trial, we send the data off, and itstays there,” says Wong. “We move on tothe next trial and the next patient andstart from scratch,” says Wong. Theyenvisioned a system that stored data onall previous patients and used advancedcomputer technology to cull informationand apply it to the planning and treatmentof each individual patient. Instead of relying only on their specific patient ortrial experiences, radiation oncologistscould now use data from all those patientsto improve the treatment of new patients.

Most adults make better decisions thanchildren, largely because they have yearsof life experience to call upon—memoriesof things they’ve done; what worked, andwhat did not. In many ways, the systemthat Taylor, Wong, and McNutt havedevised is simply a grander, technology-based form of what our brain helps us doeveryday. Now, however, physicians notonly benefit from their own experienceswith patients but also with the experiencesand results of countless physicians andpatients, avoiding what does not workand zeroing in on what does.

a computer representation, and use it toplan an intervention. Then use computer-based technology to help a surgeon carryout this plan and to assess the results.”His years in electronic manufacturinggave him the industry contacts andknowledge to develop and outfit a uniquelaboratory—one that could not only createinnovative approaches for challengingmedical problems, but carry themthrough from inception to production.

His years in industry also taught Taylorthat information is never wasted. “In man-ufacturing, we save all of the data. Whenyou have a problem, you go back and figureout how a process variation can fix theproblem,” says Taylor. His goal is to bringthis kind of data mining to medicine.

Radiation oncology physicist JohnWong was of a similar mind. Taylor wasone of the first people he sought out whenhe came to Johns Hopkins seven yearsago. The two agreed that delivery of medical care should be more informationdriven, and Radiation Oncology, with

director of quantitative sciences, to betterunderstand how cancers spread. By com-paring tumor samples from several sitesof metastasis to samples of normal tissue,Salzberg hopes to quantify the accumulatinggenetic mutations and determine theorder in which the tumors occurred, pro-viding a schematic for how a particularcancer progressed. “Perhaps we can helpcancer researchers get a better handle onthe course of metastasis,” says Salzberg.

Salzberg perhaps most succinctlyexplains the value of the engineering and cancer researcher collaboration.Engineers are the technology experts, he says, and physicians and scientists are the disease experts. Both are needed toconquer difficult problems like cancer.“Cancer is complicated,” he says, “buttogether we might figure it out.”

COMPUTER-ASSISTEDINTERVENTIONSAfter working for 19 years as a researchmanager at IBM, engineer Russell Taylorbecame interested in the role of computersand robots in surgery and medicine. Herecognized that the same combination ofinnovation , computers, and technologythat revolutionized the electronics industryhad the potential to do the same for healthcare. Taylor decided that if he wanted topursue medical applications, he ought to bein the same place as his customers. Hecame to Johns Hopkins in 1995 and focusedhis efforts on building an engineeringresearch laboratory that used computers,robots, and information-based technolo-gies to help plan, carry out, and assess newtreatments for a variety of diseases, includ-ing cancer. The concept earned him $33million in seed funding from the NationalScience Foundation to begin the Center forComputer-Integrated Surgical Systemsand Technology, which opened in 1997.

Taylor’s philosophy combines practicalbusiness sense with forward-thinking science. “Start with everything you knowabout the patient, including images, labresults, and clinical data, and add in whatyou know in general about people anddiseases based on statistics and anatomy,”says Taylor. “Combine all of this to make


COMPUTERS, ROBOTS, SENSORS, IMAGINGDEVICES AND GUIDANCE SYSTEMS INTERFACEWITH CLINICIANS SO THEY MANEUVER INSIDETHE BODY WITHOUT OPENING PATIENTS UP.

John Wong


S272011/2012 PROMISE&PROGRESS

SHE WAS WALKING down the steps athome when her leg suddenly gave way.Her mother, Clara, knew something waswrong when her doctor didn’t even ask for an x-ray. Instead the family was sentstraight to Johns Hopkins Hospital, wherethey learned Carla had bone cancer knownas osteosarcoma. To cure the cancer growing inside the femur bone in her leg,doctors would have to amputate her leg.

For anyone this would be difficult toaccept, but for a vibrant young high schoolstudent like Carla, who loved to dance, it was unimaginable. Still Carla was brave.“The leg has to go,” she said.

The knowledge that she would be losing part of her leg was hard enough, butthe reality of life without it was even moredifficult. She imagined a prosthetic leg thatwould look much like her real leg. Instead

she woke to find a metal rod with a footattached. As if cancer was not hardenough for the teen to cope with, Carlanow had to face the new physical and emotional challenges of adjusting to lifewith a prosthetic leg—and one that to herand her family seemed subpar.

The medical care at Johns Hopkins hadbeen excellent, and the family was thankfulfor that. Fitting Carla with an appropriateprosthetic was another matter. To returnto the person she had been before the cancer—before cancer took her leg—sheneeded a better prosthetic leg.

Carla’s mother Clara was serving in themilitary and decided to take Carla to theWalter Reed National Military MedicalHospital. With the country at war, the military had become an expert in prosthet-ics. It turns out that one of the military’scollaborators in improving prosthetics wasengineers at the Johns Hopkins AppliedPhysics Laboratory (APL).

In 2009, the APL was awarded a $30.4 million contract under the DefenseAdvanced Projects Agency RevolutionizingProsthetics Program, an ambitious effort toprovide the most advanced medical andrehabilitative technologies for military per-sonnel injured in the line of duty. Amongtheir projects is a next-generation mechan-ical arm that mimics the properties andsensory perception of the real thing.

Clara told the staff at Walter Reed, “I needmy daughter to have what the soldiers have.”

Carla still had difficult challenges toface. The loss of Carla’s limb made her avisible representation of illness. When shereturned to school she faced teasing by afew mean-spirited students. However, overtime things began to change. With the helpof her new, state-of-the-art prosthetic andthe doctors at Walter Reed, Carla began towalk easily and fluidly, without pain.

The real turnaround, however, came thefollowing summer when Carla decided toattend Amputee Coalition of America’s(ACA) youth camp. Carla rememberssmiling when she arrived at the camp.“I realized I wasn’t the only one goingthrough this. There were kids missingone leg, two legs, and arms. They wereamazing people,” Carla says. “I wanted to be amazing, too.”

Carla rediscovered herself. “I found I could do anything I wanted. I could be the person I was before I got sick.”Carla, a beautiful young woman withbright eyes and a warm personality, isquick to smile, even when recounting thedifficult details of her battle with cancer.“I learned I was normal,” she says. I didn’t care what people thought about myleg anymore. I was wearing skirts andshorts. I felt like a million bucks.”

Since then, Carla has faced and beaten arecurrence of her cancer. She is a patientambassador for the Kimmel Cancer Center,a volunteer at Walter Reed, and a counselorat the ACA camp. She graduated from theCommunity College in Baltimore Countyand has registered for the spring semesterin Towson University in Maryland to pursue a career in veterinary medicine.

“When I look forward in life,” Carlasays, “I see myself as a person who cantake chances, who can become a leader,who can understand what people are going through, because I’ve been through adifficult situation. People with prostheticsshould know they don’t have to feel limitedin any way. They can run, dance, ride abike, and wear heels,” says Carla. “I wantedto deal with cancer, to be a cancer survivor,and move on with my life. I’ll never forgetwhat happened, but I won’t let it affect theperson I become. Sometimes,” she says, “I forget I have a prosthetic.” •

A NEW LEG FOR CARLAOften cancer is an invisible disease. It attacks theblood or internal organs, making patients gravely ill,but leaving their outward appearance unchanged.Fifteen-year-old Carla’s situation was different.

“Rare cases, a doctor may see everytwo years,” says Wong. “But now he orshe can go back and look at certain attrib-utes of prior similar patients and make abetter informed treatment plan.” Keepingdata allows care to more quickly reflectadvances in science. “Let’s say there is adiscovery in the future that completelychanges how a cancer is staged. If that’sthe case, then all of my previous study ofthat stage won’t apply anymore,” saysWong. “But, if you keep the data, when anew discovery happens, you simply goback to the original data and recalibrate itand make it useful again.”

They have piloted their concept, calledOncospace, in head and neck cancerswhich McNutt says are very geometricallycomplex and among the most difficult cancers for radiation physicists and oncol-ogists to plan, often requiring 10 to 20 planrevisions. There is a lot of anatomy in thearea of these tumors. Critical structures,such as the voice box and salivary glands,must be spared radiation to prevent harm-ful and unpleasant side effects to patients.In their new data-mining approach, theteam analyzes the geometry of the patientand tumor. Then they go to a database ofall patients who should have been as


hard or harder to treat because of tumorproximity to critical structures and otherfactors, to come up with an optimal treat-ment plan for each individual patient. In early studies, the method considerablyimproved treatment plan quality andspared critical organs. As a result, studiesin pancreas, prostate, and other cancersare being planned.

Wong, who has worked both in medicalphysics and research and in the clinicalsetting feels strongly that advances devel-oped in the academic medical setting shouldbe put into practice everywhere. Datamining like this, he says, allows doctors ina community where they may not see asmany patients as a Johns Hopkins doctor,to call upon our data to develop bettertreatment plans for their patients.

Computer-based efforts such as this areconsidered infrastructure, not research,

and so their work is not supported by public funding. While the NationalCancer Institute has encouraged theirefforts, it will not fund it, so forwardprogress is often dependent on the abilityto find private support.

In the operating room, Taylor also isusing technology to improve treatment.Basically, Taylor says, they put a computerbetween the patient and the surgeon anduse technology to enhance his or her capa-bilities, mainly by giving the surgeon moreinformation. To do this, they engineers avariety of technologies. They use computers,robots, sensors, imaging devices, andguidance systems to interface with clinicians so that they can maneuverinside the body without opening patientsup and still clearly see and preciselymanipulate their anatomical targets.

With an impressive resume, whichincludes work on technology used in theda Vinci robotic surgical system for mini-mally-invasive surgery, Taylor is piloting

new advanced technologies that can beused in laparoscopic surgery for liver cancer, kidney cancer, prostate cancertreatment, and other malignancies.Among his inventions are high-dexterityrobotic devices that can, for example, getinto a bone where a cancer has spread andclean out tumor cells. The snake-likedevice is deployed through a tiny hollowpipe that moves around the cavity. Otherappliances, including water jets andbrushes, can be used in conjunction tohelp remove cells. The void in the bone isthen filled with a special cement to main-tain bone strength and stave off treat-ment-related fractures. These nimble,image-guided robotic devices also arebeing explored for head and neck surgerywhere surgeons must maneuver with little visibility below the vocal cords andother areas.

Cancer surgeon Michael Choti was oneof Taylor’s first collaborators. A recentproject involving Choti, radiologist EmadBoctor, and others from the center usesultrasound elastography to help Chotiimprove treatment for patients withadvanced liver cancer. For many patients,Choti can avoid cutting these tumors outby using special devices to burn or ablatelesions in the liver. The problem for Chotiand other surgeons is that there is no realquantitative measurement to let themknow that the tumor, and an adequatemargin around it, is completely destroyed.They must rely on visual observationsand generalized time recommendations.Surgeons want—to heat just what theyneed to—no more, no less, so Choti andthe other team members are piloting theelastography tool that acts as a gauge forthe firmness of tissue being heated.“Cooked” tissue will be stiff, so the newtechnology allows surgeons to direct theright amount of heat to cancerous lesions

ROBOTIC DEVICES INTEGRATE IMAGE GUIDANCEAND COMBINE TECHNOLOGIES, SUCH ASULTRASOUND AND CT , TO PROVIDE CLEARERAND MORE DETAILED PICTURES OF TUMORS

Russell Taylor


and monitor the surrounding normal tissue to prevent damage.

Taylor and team also are working withChoti and other Johns Hopkins surgeonson improving technologies to advanceminimally invasive surgery. Theseapproaches require precise and clearimage guidance because surgeons have tobe able to see their target without actuallyopening the patient up. “Targeting andmonitoring has been suboptimal and amajor roadblock to advances,” says Choti.“Our goal is to do these procedures thebest way they can be done, and our collaborations with engineers have beeninvaluable in making this happen,” saysChoti. “It brings innovation to the bedsideand helps to keep it cost effective.”

BIG SHINY OBJECT SYNDROMERadiation oncology is unique amongother cancer-related specialties in that it is completely dependent upon technologi-cally-advanced equipment, such as linearaccelerators, to deliver the precisely targeted X-ray beams that cut throughand destroy tumor cells. Patients hearadvertisements about one machine oranother, and they think if a hospital doesn’thave a particular one, they’re not practicinggood medicine. In many instances, Wong says, the information is marketingdriven, not fact-driven, and it is confusingpatients. All too frequently claims of clinical benefit are made with no scientificevidence to back it up.

In this new age of medicine-driven marketing, it is Wong’s job to help RadiationOncology and Molecular RadiationSciences director Ted DeWeese determinewhich advanced technologies are needed toimprove patient care and which are simplya product of aggressive advertising byindustry and for profit health care prac-tices. “Here with Dr. DeWeese, we do itright,” says Wong. “We don’t believe inpurchasing big, expensive pieces of equip-ment simply because it’s the newest thing out there.The truth is many of the machines actually do the same thing. The only people really benefitting are the people making and selling them. We’llexplore these technologies because we

want to be sure Hopkins tells people howto do it right,” says Wong.

Radiation treatment, Wong says, is in essence a form of minimally invasive surgery. Instead of scalpels, radiationoncologists use precisely targeted beams ofradiation to cut through tissue and tumors.The main reason there is no scientific evidence to support many of the industryclaims is that, for radiation oncology, therewas no way to do the research. “There wasno laboratory counterpart for what we doin the clinic,” says Wong. So, he called inTaylor to build a downsized version of ahuman machine for mice. It’s radiosurgeryfor mice. With unprecedented precision,Wong uses the machine to performhuman-quality radiosurgery on mice sothat he can have a realistic model to studywhat doctors do in treatment. “In radia-tion oncology, we didn’t have the means tostudy mechanisms in animals, and thismachine helps us do that,” says Wong.The miniature machine allowed Wong’smedical collaborators to uncover the causesof—and how to avoid—radiation treatment-induced bone fractures. In radiation oncol-ogy there is nearly equal interest in how todestroy tumors as there is in how to pre-vent damage to normal tissue, so beingable to study human therapies in animalmodels is paramount to developing more

effective and safer ways to treat patients. While fancy machines are often the

focus of attention, Wong says, the biggestproblem in radiation oncology often is notthe treatment technology but rather theability to characterize the tumor. “If Idon’t know where the disease is, it doesn’tmatter how great the equipment is, I can’ttreat it,” says Wong. “People at Hopkinsask, ‘What is the problem? What is thesolution?’” This, he says, is where the col-laboration between engineers and CancerCenter experts comes into play. Cancerimaging experts like Martin Pomper arehelping make cancers more visible, byengineering light-emitting pharmaceuticalsthat are specific to cancer cells to makethem glow. “Now, I can see the cancer,and not just the more obvious tumor butother cells that may be hiding,” saysWong. Taylor is building robotic devicesthat integrate image guidance and combinetechnologies, such as ultrasound and CT, to provide clearer and more detailedpictures of tumors and anatomy.

“These types of advances are unique to Johns Hopkins,” says Wong, “and theyare a direct result of the Kimmel CancerCenter and Engineering collaborations.” •

John Wong with medicalstudent Christopher Jackson

NOW ON VIDEO THE FINE PRINT OF CANCERTHE FINE PRINT OF CANCER SERIES TAKES YOU THROUGH

THE PARTS OF THIS DISEASE THAT

HAVE NOTHING TO DO WITH

TREATMENT, BUT EVERYTHING

TO DO WITH SURVIVAL.

CHEMO SCHOOLCHEMO SCHOOL IS AN INTRODUCTION TO CHEMOTHERAPY

AT THE JOHNS HOPKINS KIMMEL CANCER CENTER.

CHEMO SCHOOL IS DESIGNED TO TAKE THE FEAR OUT OF

CHEMOTHERAPY FOR BOTH THE

PATIENT AND THEIR CAREGIVERS.

FROM THEIR FIRST STEPS INTO

THE CHEMOTHERAPY ROOM TO

RECEIVING IVs, INFUSIONS OR PILLS, CHEMO SCHOOL WILL

EDUCATE AND INFORM THE PATIENT WHO IS PRESCRIBED

CHEMOTHERAPY.

PANCREATIC CANCERIN THE PANC MD V IDEO SERIES

JOHNS HOPKINS PANCREATIC

CANCER EXPERTS DISCUSS

MULTIDISCIPL INARY CARE.

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ON OUR CANCER, A BLOG

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IF YOU HAVEN’T DONE SO ALREADY, SUBSCRIBE TO

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LISTENCANCER NEWS REVIEW – PODCASTKEEP YOUR CANCER IQ CURRENT WITH K IMMEL CANCER

CENTER DIRECTOR DR. BILL NELSON AS HE DISCUSSES

THE TOP CANCER STORIES EACH MONTH.


Pancreatic CancerA PATIENT AND HIS DOCTORBALANCE HOPE AND TRUTHIn this book, pancreas cancer patient Michael J. Lippe and hisKimmel Cancer Center oncologist Dr. Dung T. Le alternate chapters. Lippe writes about the early signs that something waswrong; Le continues with a description of pancreatic cancer, its

symptoms, and its treatments.Lippe further discusses his prog-nosis, the prospect of death, andhow he began to cope, while Leexplains the importance, for bothdoctor and patient, of balancinghope and truth. Lippe talks franklyabout the toll the disease takes onhis marriage and family, and Leoffers a general picture of whatmost patients can expect with their illness. The book concludeswith Lippe and Le’s reflections on their partnership in treating

cancer, lessons they learned, and thoughts about the positivethings that sometimes emerge from illness.

Pancreatic Cancer offers clear explanations of the disease, what people with the disease will feel physically and mentally,and the current treatments and future directions of research. The authors hope that their honest yet hopeful perspective willhelp all people with cancer and those who care about them.

NCI CHOOSES JOHNS HOPKINS TO CATALOG CANCER PROTEINSThe National Cancer Institute (NCI) selected Johns Hopkins asone of eight institutions to develop a catalog of proteins createdby cancer cells. The information, which will be made available to other researchers, could be used to develop new ways to detectcancer and treat the disease.

The network, called the Clinical Proteomic Tumor AnalysisConsortium, will leverage information already revealed aboutcancer genes through the Human Genome Project and TheCancer Genome Atlas network to predict proteins produced bytumors. Principal investigator, Daniel Chan, Ph.D., professor of pathology, oncology, radiology, and urology and director ofHopkins’ Biomarker Discovery Center, says that protein signatures can be used to spot cancer or its recurrence in patientsand as potential targets for new therapies. The information canbe combined with genetic information from patients to create a complete picture of cancer.

Chan says the Johns Hopkins team will focus on ovarian cancer and expects to receive $2 million annually for five yearsfrom the NCI.

P&P

IN THE NEWSTHE LATEST CANCER NEWS from the JOHNS HOPKINS KIMMEL CANCER CENTER

NOTEWORTHY ON THE WEB



PRETTY IN PINKIn honor of Breast Cancer Awareness monththe iconic Johns Hopkins Dome was lit up inpink, a tradition which Hopkins began in 2009.

PINK PICNICBJs Wholesale Club in Owings Mills, Md.hosted a “Pink Picnic” luncheon to cele-brate breast cancer survival and honorthose who offer hope and support tobreast cancer patients and survivors. The event included talks by KimmelCancer Center Breast Cancer ProgramDirector Dr. Vered Stearns.

LEARN MORE ABOUTBREAST CANCER ONTHE WEBC-ANSWERSKimmel Cancer Center experts discussbreast cancer as part of our new videoseries C-Answers. Watch to get answersto commonly asked questions and get the latest information about advances inresearch, treatment, and clinical trials.

TOP DOCS MOONLIGHTAS GROCERY BAGGERSBreast Cancer Program Directors Drs. Sara Sukumar and Vered Stearnsserved as guest grocery baggers at

Safeway’sBoston Street,Md. location insupport of thestore’s annualbreast cancerfund raisingcampaign.Since 2003,

Safeway has donated more than $1 millionto the Kimmel Cancer Center BreastCancer Program.

BREAST CANCER AWARENESS

L to r: Deborah Stewart, Dina Klicos and Vered Stearns


NEW APPOINTMENTS AND ARRIVALSRoisin M. Connolly, M.B., BCh, B.A.O.,M.R.C.P.I., has joined the Breast Cancer program as an assistant professor of oncology.She graduated with first class honors from theMedical School in Trinity College, Dublin,Ireland where she received the Sir James CraigMemorial Prize for first place in Medicine. Shealso was awarded the prestigious ReubenHarvey Prize by the Royal College of Physiciansin Ireland for first place nationally in Medicine,Surgery and Obstetrics. At the Kimmel CancerCenter, she will focus on drug development and clinical trial design, and will establish acontinuity outpatient clinic where she will seepatients with breast cancer.

Russell Hales, M.D., has joined the Departmentof Radiation Oncology and Molecular RadiationSciences as an instructor. He is focusing onclinical and research efforts in thoracic malignancies, including developing a thoracicmultidisciplinary clinic and participating in the development of the Lung Cancer Center ofExcellence at Johns Hopkins Bayview. Hisresearch interests include novel radiation sensi-tizers in non-small cell lung cancer and charac-terization of organ motion in thoracic tumors.

Danijela Jelovac, M.D., was appointed anassistant professor of oncology. Danijela is aclinical investigator specializing in women’scancers, most specifically, breast and femalereproductive cancers. She has joined theKimmel Cancer Center as an assistant professorof oncology and will treat patients primarily at our Bayview campus. She completed a post-doctoral research fellowship with aromataseinhibitor expert Angela Brodie, Ph.D, at theUniversity of Maryland and recently finishedher fellowship at the Kimmel Cancer Center,working with Dr. Deborah Armstrong andother members of our Breast Cancer Program.

Ronan J. Kelly, M.D., has joined the UpperAerodigestive Program as an assistant profes-sor of oncology. He was recruited from theNational Cancer Institute (NCI) where he was athoracic oncology clinical investigator, writingand directing a number of innovative investiga-tor-initiated clinical trials. In addition to hiswork at NCI, Kelly served for two years as theMedical Director at Roche Pharmaceuticals in Ireland. At the Kimmel Cancer Center, hewill continue his research in lung cancer andcancers of the thymus gland and tissue andbegin researching esophageal cancer.

Jenny Kim, M.D., instructor in oncology, is a new member of the Genitourinary CancerProgram and will focus on developing a clinicalresearch program, including personalized med-icine strategies, for kidney and bladder cancers.Her research accomplishments include workwith Dr. Brian Rini, an international expert onkidney cancer drug development.

Evan J. Lipson, M.D., will be working in cancerimmunology as a new instructor in oncology.His long-term goal is to develop translationalclinical strategies to treat melanoma, focusing onimmunotherapies, including melanoma vac-cines and immune-modulating monoclonalantibodies, and molecularly targeted agents. Hewas selected to be the Chief Fellow in 2010 andhas spent the past two years training in clinicalresearch in melanoma with Drs. WilliamSharfman and Suzanne Topalian.

Eric Raabe, M.D., Ph.D., an instructor inoncology in the Division of Pediatric Oncology,will work as a physician-scientist focusing onpediatric brain tumor research and treatment.After spending a year working in Africa as partof the Baylor International Pediatric AIDSInitiative, he came to Johns Hopkins as a pedi-atric oncology fellow. Working in the laborato-ry of Dr. Charles Eberhart in Neuropathology,Raabe successfully established a human neuralstem cell system to create genetically accuratemodels of pediatric brain tumors. He will con-tinue his research and will also work closelywith Dr. Kenneth Cohen, Clinical Director ofPediatric Oncology and brain tumor expert.

IN THE NEWS


Rachel Rau, M.D., is a new member of thePediatric Oncology Program. A physician-scientist, she will focus on translational child-hood leukemia research. She completed herresidency and fellowship at Johns Hopkins andwas selected as chief resident of the Hopkinspediatric residency program and chief fellow ofthe Hopkins/NIH pediatric oncology fellowshipprogram. Rau has been conducting research inthe laboratory of pediatric oncology leukemiaexpert Dr. Patrick Brown and will continue tostudy the unique biology of leukemias with theaim of identifying new therapeutic targets.

Zeshaan Rasheed, M.D., Ph.D., has joined theGastro-intestinal Cancer Program as an assis-tant professor of oncology. He recently completedhis medical oncology fellowship at the KimmelCancer Center and was recruited to develop atranslational laboratory program focused onpancreatic cancer stem cells and their role inpancreatic cancer development and progres-sion. His fellowship work in the laboratory of William Matsui last year earned him recognition as the first and only recipient of thenew AACR “Pathway to Leadership” award inpancreatic cancer in 2010. In addition, he wasnamed a Viragh Clinical Research Scholar andwill continue to participate in the PancreaticMultidisciplinary Clinic, the outpatient clinicand inpatient service.

Kristin Redmond, M.D., M.P.H., instructor in oncology, has the joined the Department ofRadiation Oncology and Molecular RadiationSciences. She is a member of the StereotacticSpine Program and focuses on diseases of thespine and central nervous system.

Dipali Sharma, Ph.D., associate professor ofoncology, is a new member of our BreastCancer Program. She is a leading translationalscientist in the field of obesity and cancerresearch and will lead the Center’s researchefforts to further understand the connectionbetween obesity and cancer and develop prevention strategies. Her work focuses on the molecular and hormonal mechanismsunderlying the obesity-cancer connection, andshe has established important links betweenadipocytokines (cell-to-cell signaling proteinssecreted by body fat) and cancer progression.

Thomas Smith, an international leader in thefield of palliative care, has been named thedirector of Palliative Care for Johns HopkinsMedicine and the inaugural Harry J. DuffeyFamily Professor of Palliative Care in theDepartment of Oncology. He will lead palliativecare efforts throughout Johns Hopkins, includingthe Kimmel Cancer Center. His research focuseson neuropathic pain, care at the end of life, and bending the cost curve in patients with life-limiting conditions.

Chenguang Wang, Ph.D., has been appointedan assistant professor of oncology in theDivision of Biostatistics and Bioinformatics.As a statistician, he has a strong background in oncologic clinical research, particularly inclinical trials and observational studies. His current research focuses on the analysis of longitudinal data subject to “missingness,” or where there are missing values in data.Before joining Johns Hopkins and completinghis doctorate, he was a statistician with theChildren’s Oncology Group’s (COG) Statisticsand Data Center at the University of Florida andthe Center for Devices and Radiological Healthat the U.S. Food and Drug Administration.


HONORS AND AWARDS

Kimmel Cancer CenterDeputy Director andleading epigeneticsexpert Stephen Baylin,M.D., received theAmerican CancerSociety’s highest

recognition, the Medal of Honor Awardfor his basic research and pioneeringbody of work in cancer epigenetics.

Pediatric oncologistPatrick Brown, M.D.,received a four-year,$720,000 grant from the American CancerSociety for his researchexploring epigenetic

therapies for childhood leukemia.

Kimmel Cancer Center nurse LaurieBryant, R.N., was named a 2011 finalistfor the Daily Record’s Health Care Heroes

Award. She was recog-nized as a mentor toundergraduate studentsinterested in medicine,medical students,interns and residents,teaching them clinically

and modeling the important role of nursesin defining problems and recommendingcare. She has also started one of the mostsuccessful unit-based volunteer programsat Johns Hopkins.

The Society of Neuro-Oncology honoredPeter Burger, M.D., with its LifetimeAchievement Award recognizing hismore than 35 years of contributions to the field of neuro-oncology.

Michael Carducci,M.D., received the Michaele ChristianOncology DevelopmentAward in honor of his contribution to thedevelopment of novel

agents for cancer therapy.

Andrew Ewald, Ph.D., received theAmerican Association of AnatomistsMorphological Sciences Award and willpresent an award lecture at the group’sannual meeting. The award recognizesEwald’s advances in the understanding of the cellular and molecular basis of thegrowth, remodeling, and cancerous trans-formation of epithelial tissues, cells thatcover the surface of virtually every organand structure in the body.

Kimmel Cancer Center TranslationalResearch Director and pancreas cancerexpert Elizabeth Jaffee, M.D., Ph.D.,appeared on the Dr. Oz show to discussadvances in pancreas cancer research andher vaccine studies.

The Department of Defense CongressionalDirected Medical Research Programs presented Robert Kurman, M.D., with

a $9.5 million OvarianCancer ResearchProgram ConsortiumAward. The Consortiumis a major multi-institu-tional collaborativeresearch effort aimed

at identifying and characterizing early cellular changes associated with ovariancancer.

Lana De Souza Lawrence, M.D., receivedthe ASCO Conquer Cancer FoundationBreast Cancer Symposium Merit Award.The award, which includes a $25,000grant, recognizes researchers’ contribu-tions to progress against breast cancer,was given to De Souza Lawrence for herresearch on triple-negative breast cancer.

Robert Miller, M.D., and Julie Brahmer,M.D., were recipients of the 2011 AmericanSociety of Clinical Oncology (ASCO)Statesman Award. The award recognizesASCO members for extraordinary volun-teer service, dedication and commitment.

Barry Nelkin, Ph.D.,was awarded a $1.2 million grant from theAmerican CancerSociety for his researchon the development,genetic characteriza-

tion, and application of new scientificmodels for medullary thyroid cancer.

Kimmel Cancer Center director WilliamNelson, M.D., Ph.D., was one of only twoinvestigators to receive the A. DavidMazzone-Prostate Cancer FoundationChallenge Award aimed at acceleratingscientific discovery and new treatmentsfor prostate cancer. Nelson was recognizedfor his innovative research on the reversalof gene silencing. The award includes afive-year, $5 million research grant.

Martin Pomper, M.D., Ph.D., was namedthe William R. Brody Professor of Radiology.Pomper is the inaugural recipient of this professorship, designated for a radiologist physician scientist who excelsin translational innovation in imaging.

Pediatric Oncology clinician-scientist Eric Raabe, M.D., Ph.D., received a three-year, $330,000 grant from the St. Baldrick’s Foundation to support his research of Pediatric brain tumors.

IN THE NEWS


Richard Roden, Ph.D., received the VFoundation Translational Research Grantwhich includes a three-year, $600,000grant. The grant is aimed at transformingbasic scientific discoveries into clinicalapplications, such as new diagnostics andtreatments.

Charles M. Rudin, M.D., Ph.D., receivedthe 2011 Caring for Carcinoid Foundation-

AACR Grants forCarcinoid Tumor andPancreatic Neuro-endocrine TumorResearch. The two-year, $250,000 grantwill support Rudin’s

research of novel therapeutic approachesfor carcinoid tumors and pancreatic neuroendocrine tumors.

Lillie Shockney, R.N., B.S., M.A.S.,received the Amoena Corp. award for“Outstanding Contribution to the BreastCenter Industry. Amoena Corp. is awomen’s wellness company focused onhelping women following breast surgery.Shockney also was inducted into the Nu Beta Chapter of the Sigma Theta TauInternational Honor Society of Nursing.She was named editor-in-chief of theJournal of Oncology Navigation andSurvivorship, a new journal for nursesimplementing strategies in patient navigation and survivorship care.

Kimmel Cancer Center Senior Director ofDevelopment Ellen Stifler was named amember of the Senior Management Teamfor the Fund for Johns Hopkins Medicine.

Sara Sukumar, Ph.D., won a BioMarylandLIFE Prize, which includes a $50,000

award, for her discov-ery of methylated genebiomarkers that maybetter predict howpatients whose breastcancers are estrogenreceptor (ER) negative

will respond to various treatments andpotentially if they are at risk for futurerecurrences.

The National Institutes of Health Centerfor Scientific Review appointed ConnieTrimble, M.D., to a four-year term on its Cancer Immunopathology andImmunotherapy Study Section. Trimblewas selected based on her achievementsin cancer immunology and will reviewand make recommendations on grantapplications submitted to the NIH andsurvey the state of immunology research.

Victor Velculescu, M.D., Ph.D., receiveda Paul Marks Prize for Cancer Research.

The award recognizesyoung investigatorswho have become lead-ers in cancer researchthrough significant con-tributions to the under-standing of cancer.

The Brupbacher Foundation in Zurichpresented Bert Vogelstein, M.D., with

its Charles RodolpheBrupbacher Prize forCancer Research. Theprize is given bienniallyto a scientist “interna-tionally acknowledgedfor meritorious

achievements in the field of fundamentalresearch.” Vogelstein was selected for hispioneering research of colon cancer devel-opment. Vogelstein also has been namedone of the Johns Hopkins University’s 17 inaugural Gilman Scholars. The newlycreated designation, named for theUniversity’s visionary first PresidentDaniel Coit Gilman, recognizes individu-als who are exemplars of the highestideals of the university, demonstratedthrough a record of distinguishedresearch, artistic and creative activity,teaching and service.

The V Foundation awarded VasanYegnasubramanian, M.D., Ph.D., its

Martin D. Abeloff,M.D., Scholar Award.The award, whichincludes a two-year$200,000 grant, supports his research to identify DNA-based

biomarkers that can help risk-stratifymen with prostate cancer and aid in the clinical decision-making.


PHILANTHROPYGIFTS AND DONATIONS to the JOHNS HOPKINS KIMMEL CANCER CENTER

FINGERPRINTINGCANCERCOMMONWEALTH FOUNDATION GIFT CREATES NEW CENTER FOR PERSONALIZED CANCER MEDICINEA $30 million gift to Johns Hopkins from theCommonwealth Foundation for Cancer Research will push the pace of developing targeted therapiesbased on an individual cancer patient’s genetic “fingerprint” by establishing a Center forPersonalized Cancer Medicine.

The gift will be used to support innovative research and new technologiesthat pinpoint the unique cellular characteristics of each patient’s cancer.Targeting these alterations will improve treatment outcomes, thwart cancersbefore they develop and slash the costs of new drug discovery.

Johns Hopkins scientists have led the field in deciphering the genetic land-scape of cancer and uncovering key genetic mutations and pathways. Thiswork has had immediate application to patient care. For instance, a test calledPARE or personalized analysis of rearranged ends, not only detects cancerbut also can tell if a therapy is working by measuring, in real time, theamount of cancer DNA in the bloodstream. The personalized test can tell if aperson is cured with surgery or if there are cancer cells left behind and willrequire additional treatment.

“This is a watershed moment,” says Kimmel Cancer Center DirectorWilliam G. Nelson. “With this gift from the Commonwealth Foundation,we’re poised to change cancer medicine.”

Funds for the new Center will initially support three pilot projects over fouryears focused on genetic research from changes to the genes themselves tochanges to the DNA inside genes, known as epigenetics, are aimed at betterdiagnosis, treatment and even prevention. Investigators will examine whichgenomic and epigenomic determinants impact responses to treatment inpatients; study individualized early detection of human cancers by developingclinical tests that use genetic and epigenetic changes as markers for early diag-nosis; and individualized immunotherapies using the specific genetic makeupof each patient’s tumor.

The Center will include cancer experts from many disciplines at JohnsHopkins such as oncology, engineering, public health and surgery. Nelsonindicated that a hallmark of Johns Hopkins is collaboration across specialties.A recent gift to Johns Hopkins University to support an individualized healthinitiative at Malone Hall will enhance efforts in the Center for PersonalizedCancer Medicine.

“The convergence of brilliant scientific minds with this significant gift hasbrought us to a point where we can alter the course of cancer in ways we couldonly imaging just a decade ago,” says Nelson.


BOBBIE BURNETT’S ANGELS“MAKING A DIFFERENCE”Bobbie Burnett and the Caring Collectionwere recently featured in an NBC Nightly

News segment called“Making a Difference”.Bobbie and her dedicat-ed group of volunteers,who have been makingand selling stainedglass angels since 1982,were recognized for

their work in bringing hope and comfortto cancer patients and families around theworld, and for donating proceeds of nearly$1 million to the Kimmel Cancer Centerand other Maryland institutions. Learnmore about the Caring Collection atwww.caringcollection.org.

ONE NIGHT, ONE SHOW, ONE CAUSEThe Baltimore Sound Stage was the site ofthe annual benefit concert hosted by PRSGuitars and featured an amazing eveningof entertainment, including alternativerock band Vertical Horizon, Davy Knowlesof Back Door Slam, Dave Weiner of theSteve Vai Band, blues guitarist DonnaGrantis, the Paul Reed Smith Band, andour own Kimmel Cancer Center directorWilliam Nelson. Dr. Nelson traded hislab coat for a guitar and appeared on stageas a guest artist. Six PRS guitars, auto-graphed by the Baltimore Ravens and othercelebrities, were given as door prizes to afew lucky attendees. Several more guitars,embellished with original designs by localartists, were auctioned at the event.

One Cause is the flagship benefit concertof PRS Guitars. Since 2000, PRS Guitarshas raised more than $2 million for theKimmel Cancer Center’s Living withCancer Resource Program, which providesfree supportive care programming andeducation to patients and families.

THE FRIENDS OF SKIP VIRAGHHELPING FIGHT PANCREAS CANCERCarl Verboncoeur considers some of thebest times of his life the years he workedside by side with Skip Viragh at RydexInvestments. He still clearly recalls theRydex founder A. P. “Skip” Viragh, Jr.’shard fought battle with pancreas cancer, a disease that ultimately claimed Viragh’slife. Verboncoeur, who once served asRydex CEO, says he wanted to do some-thing to honor his boss and friend and to give back to Johns Hopkins whoseresearchers and clinicians work so hardto fight the disease. He and his wife Lynn started the Friends of Skip ViraghMemorial Fund and are supporting thestudies of leading cancer pancreas expertsElizabeth Jaffee and Daniel Laheru.“Johns Hopkins is on the forefront of pancreas cancer research and care,” saysLaheru, “and generosity like this gives usthe means to explore novel therapies thatmay improve the lives of patients fightingthis disease.”

BREAST CANCER SUPPORTSusan G. Komen for the Cure MarylandExecutive Director Robin Prothropresented Antonio Wolff, M.D., with a$75,000 check to support breast cancerclinical trials

SIDNEY KIMMEL’S COMPANY MAKES MULTIMILLION GIFT TO KIMMEL CANCER CENTERThe Jones Group honored Sidney Kimmel, its Founder and Chairman,

with a $6 million donation to the Kimmel CancerCenter to mark the 40th anniversary of his foundingthe company.

In recognition of Mr. Kimmel's accomplishmentsand contributions to the company, including hismany years of outstanding leadership, the Board ofDirectors announced that the company will donate

$8 million to support his many charitable initiatives, including a$6 million donation to the Kimmel Cancer Center.

William Nelson

Burnett

Kimmel

Lynn and Carl Verboncoeur


PHILANTHROPY

“We're the ones leading the way—finding the genes, studying what they do in terms ofthe biology of a particular pediatric cancer, and developing molecularly targeted therapyagainst it,” says Donald Small, M.D, Ph.D, Kyle Haydock Professor and Director ofPediatric Oncology.

For the first time in the history of cancer medicine, the technology exists to quicklydecipher the cellular causes of every cancer. Kimmel Cancer Center researchers havepioneered the science that has led us here and were the first to crack the genetic code of a pediatric cancer. Through collaborations with Johns Hopkins engineers, we aredeveloping the technologies and methods needed to manage the immense amounts ofdata this research generates and apply it to cancer medicine. What we learn, will allowus to target the very biological mechanisms that cause a cancer to grow and spread.With these discoveries, we can begin to alter the course of pediatric cancers in ways wecould only image a decade ago. There is much to be hopeful about.

Our goal is to create a $30 million research fund to ensure that these promising initiativeshave the steady support they need to result in monumental leaps in knowledge, and ulti-mately cures for all children with cancer.

We could: • find cures for those cancers we

currently cannot cure.• improve therapies, develop targeted

therapies that kill the cancer withoutharming the child.

• use biology and laboratory discoveriesto improve clinical trials.

• study the short- and long-term consequences of cancer and cancer therapy on the child to improve the quality of life during and after treatment.

Just suppose you could help a childwith cancer. You can. Learn more atwww.HopkinsMedicine.org/KidsCancer

JUST SUPPOSEA CAMPAIGN TO CURE CHILDHOOD CANCERHELPING US TURN RESEARCH INTO RESULTS—AND RESULTS INTO REALITYCancer strikes more than 12,000 children and teens each year. While pediatric cancers are rare, theyclaim the lives of more children than any other disease. But, there is good news. At Johns Hopkins,we understand the urgency that pediatric cancers demand. The Pediatric Oncology Program of theJohns Hopkins Kimmel Cancer Center is focused entirely on the research and treatment of childhoodcancers. As one of the leading Cancer Centers in the United States, we are at the forefront of developingnew treatments and designing clinical trials. With world-class expertise, a culture of cross-disciplinarycollaboration and a proven track record of successfully bringing therapies from the laboratory topatients, our researchers are leading the field in developing treatments and cures for childhood cancer.

GO TO WWW.HOPKINSMEDICINE.ORG/KIDSCANCER TO LEARN MORE ABOUT JOHNS HOPKINS PEDIATRIC ONCOLOGY.


SWIM ACROSS AMERICA BALTIMOREThe Baltimore swim held September 18 had more than 600 swimmers and raised more than $525,000 to support the SwimAcross America (SAA) Laboratory at the Kimmel Cancer Center.The event was held at the Meadowbrook Aquatic and FitnessCenter in Baltimore and included Olympians Tara Kirk, WendyWeil Weinberg, Brenda Borgh Bartlett, Craig Beardsley, JanelJorgensen, and Theresa Andrews. Despite the open water swimrelocating to the pool because of storm runoff, the event was ahuge success. Money raised will support cutting edge cancerresearch in the SAA Laboratory, directed by Luis Diaz, M.D.,including a study examining the use of circulating tumor DNA todetect and monitor more than a dozen types of cancer.

Take a virtual tour of the Swim Across American Laboratory atwww.hopkinskimmelcancercenter.org

PANCREAS CANCER RESEARCHERNAMED EVERETT AND MARJORIEKOVLER PROFESSORScott E. Kern, M.D., was named as the inaugural Everett andMarjorie Kovler Professor of Pancreas Cancer Research. Kern,professor of oncology, is co-director of the Kimmel Cancer CenterGastrointestinal Cancer Program. With more than 20,000 journalcitations, his pioneering studies of pancreas cancer are widelyrecognized. His research is the basis of a number of U.S. patentsand novel and ongoing therapeutic trials for pancreas cancer atthe Kimmel Cancer Center and other cancer centers.

The Kovler Professorship was established by the Blum-KovlerFoundation and foundation Chairman Peter Kovler. It is believedto be the first professorship endowed specifically for pancreascancer research. “Pancreas cancer does not receive the attention,financially or scientifically, that it should,” said Peter Kovler,whose mother Marjorie Kovler, died of pancreas cancer in 1970 atjust 49. The Professorship is named for and memorializes her andhis father Everett Kovler. He chose Johns Hopkins, he said,because of Scott Kern and the dedication and excellence of his sci-entific team. “If Hopkins perceives pancreas cancer as important,then others might follow, and pancreas cancer research mightbecome a scientific priority,” says Kovler.

“Scott is a research-oriented pathologist, bringing togethermolecular biology and pathology to fight pancreas cancer,” saysWilliam G. Nelson, M.D., Ph.D., Director of the Kimmel CancerCenter. “We hope this generous support from the Kovler familywill mark the beginning of the end of pancreas cancer.”

L to R: Swim Across America Laboratoryinvestigators Luis Diaz, Dung Li,Mathias Holdhoff, and Kimmel CancerCenter Director William Nelson

L to R: Dean Edward Miller, Bert Vogelstein, Scott Kern, Mr. and Mrs. Peter Kovler, WilliamNelson, President Ronald Daniels

ONLINE OPTIONS


HOW CAN YOU HELP? SEE HOW

FINANCIAL CONTRIBUTIONS CAN BE

EASILY, AND SECURELY, APPLIED.

GO ONLINE FOR MORE INFORMATION.

AVON WALK The 2011 Avon Walk, held in Washington,D.C., had 2,200 participants and raised more than $5 million tosupport breast cancer research. The Kimmel Cancer Center wasone of nine organizations awarded a grant. Our Avon BreastCenter, designated an Avon Comprehensive Breast Cancer CareCenter of Excellence, received $750,000 to support breast cancerresearch and access to care programs.

Breast cancer expert Dr. Ben Ho Park (center)amid an ocean of pink at the 2011 Avon Walk.


PHILANTHROPY

RED CARD CANCER & DC UNITEDBRING SOCCER CLINIC TOBALTIMOREOver 150 children from Baltimore City Public Schools attended aRed Card Cancer soccer clinic hosted by Baltimore City CouncilPresident Jack Young and D.C. United, raising awareness aboutthe benefits of a healthy lifestyle and exercise.

Kimmel Cancer Center Director William Nelson with D. C.United players, Santino Quaranta, Clyde Simms, Perry Kitchen,Brandon Barklage, Joseph Ngwenya took the field to run drills with the children assembled from public schools all over Baltimore City. In addition to the professional players from D.C. United, collegiate players from Loyola University and theUniversity of Notre Dame of Maryland also assisted at the clinic.

“We’re proud that Red Card Cancer is teaming up with DCUnited during its Community Soccer Clinic right here in our hometown of Baltimore to raise awareness about cancer so that togetherwe can kick cancer out of the lives of everyone,” said Nelson.

Learn more at www.redcardcancer.org

L to R: D.C. United President Kevin Payne, Baltimore CityCouncil President Jack Young, Baltimore City CouncilmanJim Kraft, Kimmel Cancer Center Director William Nelson,and D.C. United Captain Santino Quaranta

HYUNDAI HOPE ON WHEELS DONATESBaltimore Area Hyundai Dealers and Hyundai Hope onWheels selected David Loeb, M.D., Ph.D., to receive the HopeGrant, a $100,000 award to support his sarcoma research.Heather Symons, M.D., was named a Hyundai Scholar andreceived a $60,000 award to support her research of novelimmunotherapies for patients with high-risk hematologic andsolid tumor malignancies.

Hyundai Hope on Wheels is the united effort of HyundaiMotor America and its more than 800 dealers across the U.S. toraise awareness about childhood cancer and to celebrate thelives of children battling the disease.

ST. BALDRICK’S FOUNDATION Pediatric Oncology clinician-scientist Eric Raabe, M.D., Ph.D.,was named a St. Baldrick’s Pediatric Neuro-oncology Fellow

receiving a three-year grant totaling$330,000 to support his work onpediatric brain tumors.

The award was given by the St. Baldrick’s Foundation, a volunteer-driven charity committedto funding the most promising research to find cures for childhoodcancers and give survivors long and healthy lives.

PEDIATRIC CANCER UPDATEEach year, Giant associates and customers join together to fightpediatric cancer through its Triple Winner Program. The programhas raised more than $4.75 million for pediatric cancer research atthe Kimmel Cancer Center.

Triple Winner is a scratch card game, and every $1 dollardonation helps fight kid’s cancer and provides participants thechance to win a free product, gift card, or cash prize up to $10,000.

Thanks GIANT Foodfor supporting cancer research for kids!Johns Hopkins Pediatric OncologyHopkinsMedicine.org/KidsCancer

Symons (L) receivesgrant from Hyundairepresentatives

Your own vision for the future can bring a brighter tomorrow

to cancer patients and their families. Your gifts to the Sidney

Kimmel Comprehensive Cancer Center at Johns Hopkins will

help ensure that these individuals will benefit from progress

in cancer research, treatment, and education.

The Kimmel Cancer Center provides both the most advanced, compassion-

ate treatment and the world-class research – translated to the bedside – that

will ultimately defeat cancer.

Outright gifts of cash or appreciated securities are always welcome, and may

bring significant tax advantages to you.

Planned gifts – such as charitable trusts – provide income to you for life,

as well as considerable tax benefits, while helping to ensure the continuing

leadership of the Kimmel Cancer Center at Johns Hopkins.

A bequest to the Kimmel Cancer Center in your will ensures that your vision

will be carried out, and may also reduce the estate tax liability of your heirs.

A man has made at leasta start on discoveringthe meaning of humanlife when he plantsshade trees underwhich he knows fullwell he will never sit.— David Elton Trueblood

For more information, please contact:

Christine A. Lambert, Esq.

Johns Hopkins Office of Gift Planning

800-548-1268 or 410-516-7954e-mail: [email protected]

or visit: www.plannedgifts.org/jhu/

One North Charles Center100 N. Charles StreetSuite 234Baltimore, Maryland 21201

KIMMEL CANCER CENTER ON THE WEB

Read more about our science, watch videos, and more at www.hopkinskimmelcancercenter.org

ENGINEERING CURES

For additional copies of this publication or furtherinformation about the Kimmel Cancer Center, please call (410) 955-1287 or email [email protected]

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