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A Cancer To-Do List

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Science  25 Oct 2013:
Vol. 342, Issue 6157, pp. 418
DOI: 10.1126/science.342.6157.418

The current climate of austerity has not stopped NCI Director Harold Varmus from launching new initiatives.

Even as National Cancer Institute (NCI) Director Harold Varmus contends with tight budgets (see main story, p. 416) he has an unusually long list of priorities.

Provocative Questions

Target.

Pancreatic cancer cells are usually driven to grow by mutations in RAS genes.

CREDIT: STANLEY FLEGLER/VISUALS UNLIMITED INC.

Why does obesity increase cancer risk? Why are some cancers easily cured with conventional chemotherapy? Those are among about two dozen little-explored or neglected cancer puzzles that Varmus wants researchers to explore in NCI's Provocative Questions initiative, which has awarded $35 million in new grants since 2012 and is now taking proposals for a third round of funding.

Global Cancer

NCI's new Center for Global Health aims to help developing countries create cancer registries and national cancer plans. Another priority is to study the high rates of certain cancers in some countries—gallbladder cancer in Chile, for example.

Oncogene Initiative

Varmus is directing $10 million at NCI's large contract lab in Frederick, Maryland, to finding drugs that target the cell signaling pathway controlled by RAS, a family of oncogenes. Mutations in RAS drive uncontrolled cell growth in one-third of all cancers, so drugs blocking this pathway could help many patients. The initiative is part of an effort to revamp Frederick to focus on large goal-oriented projects, following the model of the Department of Energy's major research labs.

The Cancer Genome Atlas

The Cancer Genome Atlas (TCGA), a $375 million sequencing project launched with the National Human Genome Research Institute 7 years ago, is winding up its analysis of major mutations in 10,000 tumor samples covering about 20 cancer types. One of TCGA's original proponents, Varmus says NCI will soon launch a cloud computing pilot project to support further data mining.

Unconventional Trial

NCI plans to genotype the tumors of about 1000 patients who are no longer helped by conventional treatments and match them with an experimental drug aimed at a mutation in the patient's tumor. NCI has assembled a medicine chest of about 30 drugs contributed by a dozen companies. This "unconventional" clinical trial is "one way to dramatically extend our efforts to explore new therapies with genetic tools," Varmus says.

Exceptional Responders

Varmus has asked the research community to comb through their records for rare cases in which a patient's cancer shrank or disappeared in response to a drug that failed to help most patients. The goal is to learn whether specific genetic defects in the patient's tumor can explain such exceptional responses.

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