Sequencing Cancer

This month’s AACR attendees, including National Cancer Institute Director Harold Varmus, discuss new approaches to cancer research using whole genome sequencing.

By | April 9, 2013

ISTOCK, ALENGOIn a special lecture presented at the American Association for Cancer Research (AACR) meeting on Monday, April 8, National Cancer Institute (NCI) Director Harold Varmus discussed two new models of cancer research. The first, dubbed phenotype-to-genotype (P2G), capitalizes on the seemingly miraculous recoveries of a handful of patients in otherwise failed clinical trials. Known as “exceptional responders,” these patients show noticeable improvements—sometimes even complete remission—in response to a drug that did little or nothing for other patients in the trial. By sequencing the genomes of these exceptional responders, cancer researchers hope to gain clues regarding their unexpected recoveries that might help identify the subpopulations of patients for which the drug may prove most beneficial.

Jim Doroshow of the NCI’s Center for Cancer Research, elaborated on this approach, noting that the agency hopes to recruit at least 100 exceptional responders for study by institute researchers. These patients are “low-hanging fruit” for furthering drug development programs that may have been shuttered due to negative trial results, Doroshow said. “Can we look and find agents that were tried and discarded in the last 10 years, maybe even 20 years?”

NCI is also pursuing the opposite approach, known as genotype to phenotype (G2P), in which whole genome sequencing is used in large patient populations to improve the use of targeted cancer drugs and identify biomarkers of disease and drug response, Varmus described. In this light, the NCI hopes to screen as many as 3,000 patients in the next 9 months to enroll a total of 800–1,000 participants to have their genomes sequenced by a network of NCI sequencing centers around the country, Doroshow noted.

Another proponent of studying genomes in pursuit of a better understanding of cancer is sequencing guru Elaine Mardis of Washington University in St. Louis. She argued for the use of whole genome sequencing to analyze tumor heterogeneity and to track cancer’s evolution. “The presence of mutation reflects [the tumor’s] history,” she said, with variants that are present in more tumor samples representing older mutations, while newer alterations may only show up in derivative metastatic tumors, for example. She also emphasized the importance of sequencing not just DNA, but RNA as well, noting that many of the mutations identified via whole genome sequencing may never be expressed, and thus not be relevant to understand the mechanisms driving cancer progression.


Add a Comment

Avatar of: You



Sign In with your LabX Media Group Passport to leave a comment

Not a member? Register Now!

LabX Media Group Passport Logo


Avatar of: mlerman


Posts: 53

May 4, 2013

Playing with words and patients lives, no new defeat...

Michael Lerman, M.D., Ph.D.

BD Biosciences
BD Biosciences

Popular Now

  1. The Mycobiome
    Features The Mycobiome

    The largely overlooked resident fungal community plays a critical role in human health and disease.

  2. Simulating Scientific Sabotage, For Fun
  3. Antibody Alternatives
    Features Antibody Alternatives

    Nucleic acid aptamers and protein scaffolds could change the way researchers study biological processes and treat disease.

  4. Holding Their Ground
    Features Holding Their Ground

    To protect the global food supply, scientists want to understand—and enhance—plants’ natural resistance to pathogens.

Life Technologies