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A decade of cancer genome projects has provided a sober-

ing message about the complexity of this disease. Genetic

alterations contributing to tumor growth can vary among

patients, between primary tumors and metastases, and

even within dif erent regions of a single tumor. This hetero-

geneity can explain why a specifi c drug benefi ts one patient

but not another and why a patient initially helped by a medication

might later present with recurrent, drug-resistant disease.

Cancer’s genetic complexity poses a formidable challenge for

therapy, but researchers are addressing this challenge on sev-

eral fronts. There is a growing recognition, for example, that

simple changes to the dose and/or scheduling of existing cancer

drugs can delay the emergence of drug resistance. For promis-

ing drugs such as immunotherapies and tyrosine kinase inhibi-

tors, the search is on for predictive biomarkers that will help

identify the patients most likely to respond. And cancer drugs

that operate through new mechanisms of action are in the pipe-

line, exciting many in the fi eld. Among these are molecules that

target the activity of epigenetic regulators with established roles

in cancer development and molecules that selectively kill tu-

mor cells by exacerbating the detrimental ef ects of mutations.

Other molecules are fi nally reaching protein targets previously

classifi ed as “undruggable.” And as the cancer medicine cabinet

becomes better stocked, clinicians will continue experimenting

with combinations of drugs, which history has shown can be

more ef ective than treating with single agents. It will no doubt

take a complex array of therapies to defeat this complex foe.

In the world of cancer drug development,

the path from scientif c concept to

clinical ef cacy is often long and full of

unexpected twists and turns.

NEWS

When less is more p. 1144

REVIEWS

The cancer epigenome: Concepts, challenges, and therapeutic opportunities p. 1147

PARP inhibitors: Synthetic lethality in the clinic p. 1152

Drugging RAS: Know the enemy p. 1158

Waste disposal—An attractivestrategy for cancer therapy p. 1163

RELATED ITEMS

c EDITORIAL P. 1103

c POLICY FORUM P. 1131

INSIDE

By Paula A. Kiberstis and John Travis

FRONTIERS IN

CANCER THERAPYSTOCKING ONCOLOGY’S MEDICINE CABINET

17 MARCH 2017 • VOL 355 ISSUE 6330 1143

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Stocking oncology's medicine cabinetPaula A. Kiberstis and John Travis

DOI: 10.1126/science.355.6330.1142 (6330), 1142-1143.355Science 

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