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3D 'organoids' grown from patient tumorscould personalize drug screening

May 7, 2015

Cell Press

Three-dimensional cultures (or 'organoids') derived from the

tumors of cancer patients closely replicate key properties of

the original tumors, reveals a study. These 'organoid'

cultures are amenable to large-scale drug screens for the

detection of genetic changes associated with drug sensitivity

and pave the way for personalized treatment approaches

that could o timize clinical outcomes in cancer atients.

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FULL STORY

3-D organoid cultures derived from healthy and tumor tissue from

colorectal cancer patients are used for a high throughput drug screen

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Credit: van de Wetering et al./Cell 2015

Three-dimensional cultures (or "organoids")

derived from the tumors of cancer patients closely

replicate key properties of the original tumors,reveals a study published May 7 in Cell. These

"organoid" cultures are amenable to large-scale

drug screens for the detection of genetic changes

associated with drug sensitivity and pave the way

for personalized treatment approaches that couldoptimize clinical outcomes in cancer patients.

"This is the first time that a collection of cancer organoids, or a living

biobank, has been derived from patient tumors," says senior study author

Mathew Garnett, a geneticist at the Wellcome Trust Sanger Institute. "We

believe that these organoids are an important new tool in the arsenal of

cancer biologists and may ultimately improve our ability to develop moreeffective cancer treatments."

To study the causes of cancer and develop new cancer treatments, many

laboratories use experimental model systems such as cells grown from

patient tumors. However, currently available cell lines have been derived

under suboptimal conditions and therefore fail to reflect important features

of tumor cells. As a result, it has been challenging to predict the drug

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sensitivity of individual patients based on their unique spectrum of genetic

mutations.

In recent years, scientists have developed organoid cell culture systems as

an alternative approach to grow normal and diseased tissue in a dish. In

contrast to cell lines, organoids display the hallmarks of the original tissue

in terms of its 3D architecture, the cell types present, and their self-renewal

properties. Given the advantages of organoids, Garnett and Hans Cleversof the Hubrecht Institute set out to test whether these cultures could

potentially bridge the gap between cancer genetics and patient outcomes.

In the new study, the researchers grew 22 organoids derived from tumor

tissue from 20 patients with colorectal cancer and then sequenced genomic

DNA isolated from these cultures. The genetic mutations in the organoid

cultures closely matched those in the corresponding tumor biopsies and

agreed well with previous large-scale analyses of colorectal cancermutations. These findings confirm that the cultures faithfully capture the

genomic features of the tumors from which they are derived as well as

much of the genomic diversity associated with colorectal cancer.

To link drug sensitivity to genetic changes, the researchers next screened

the responses of the organoids to 83 experimental and approved cancer

drugs. Given their diverse genetic profiles, the organoids displayed a

range of sensitivities to the drugs. In validation of the approach, the

researchers identified previously reported associations between specific

mutations and resistance to particular drugs. The organoids also revealed

a novel gene-drug association, indicating that the subset of cancer patients

with RNF43 mutations would strongly benefit from a drug that inhibits a

protein called porcupine. "At some point in the future, this approach may

be suitable for modeling individual patient response to cancer therapies to

inform clinical treatment," Garnett says.

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Cite This Page:

Cell Press. "3D 'organoids' grown from patient tumors could personalize

drug screening." ScienceDaily. ScienceDaily, 7 May 2015.

.

Moving forward, the researchers plan to expand the panel of existing colon

organoids as well as develop an organoid biobank for other tumor types.

"Cancer is a diverse and complex disease and having a large collection of

organoids is necessary to encompass this diversity to enable scientists and

clinicians to develop new treatments," Garnett says.

Story Source:

The above story is based on materialsprovided by Cell Press. Note:

Materials may be edited for content and length.

Journal Reference:

1. van de Wetering et al. Prospective derivation of a Living

Organoid Biobank of colorectal cancer patients. Cell, May 2015

DOI: 10.1016/j.cell.2015.03.053

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Ebola Virus in Patients Eye Fluid 10 Weeks After It Was Undetectablein Blood

May 7, 2015 Researchers are reporting a case study in which viable Ebola

virus was present in the eyes aqueous humor the clear fluid in the front of

the ... read more

New Intervention Helps Mothers Address Depression

May 7, 2015 A new intervention has been developed that identifies

potentially depressed mothers and encourages them to seek treatment. The

Motivating our Mothers (MOM) program takes a unique approach, relying on

... read more

Ecologist Warns of Bamboo Fueling Spread of Hantavirus

May 7, 2015 The popularity of bamboo landscaping could increase the

spread of hantavirus, researchers say, with the plant's prolific seed

production creating a population boom among seed-eating deer mice that ...

read more

May 7, 2015 Much like a finger leaves its own unique print to help identify

'Fracture' Prints, Not Fingerprints, Help SolveChild Abuse Cases
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a person, researchers are now discovering that skull fractures leave certain

signatures that can help ... read more

The Opioid Epidemic and Its Impact on Orthopaedic Care

May 7, 2015 The United States makes up less than five percent of the

world's population but consumes 80 percent of the global opioid supply andapproximately 99 percent of all hydrocodone -- the most commonly ...

read more

May 7, 2015 By increasing the stiffness of erythrocytes infected by the

causal agent of malaria, Viagra favors their elimination from the blood

circulation and may therefore reduce ... read more

May 7, 2015 How safe is that robot doing your surgery? Researchers

easily hacked a next generation teleoperated surgical robot to test how easily

a malicious attack could hijack ... read more

Viagra to Prevent Transmission of the MalariaParasite?

Researchers Hack a Teleoperated SurgicalRobot to Reveal Security Flaws
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11/13

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