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ASCO: Bringing Genomics to Oncologists

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Thousands of clinicians and researchers have gathered at the 2011 meeting of the American Society of Clinical Oncology in Chicago to hear about the latest advances in cancer science and treatment. National Cancer Institute Director Harold Varmus kicked things off by talking about what NCI plans to do in the next few months. There is an opportunity to make advances against cancer, and accelerate progress in discovery, understanding disease mechanisms, and translating developments in the lab to new treatments, diagnostics, and biomarker tools, he said. Although the National Institutes of Health and NCI budgets are being cut 1 percent below 2010 levels, Varmus added that NCI still has a $5 billion budget at its disposal and is looking for the wisest ways to spend it. In particular, Varmus spoke about NCI's plan to set up a center for cancer genomics, which would have a mission of bringing the latest advances in genomics to cancer research and care. Varmus also said he was concerned that in a time of fiscal restraint, researchers would be tempted to study the obvious instead of delving into the questions that are more interesting, but harder to answer, such as the link between cancer and obesity, and the question of why aspirin helps protect against certain cancers. He encouraged the audience to keep thinking in new ways, and said NCI is requesting proposals for novel and promising ways to address some of these interesting questions. "We all know we could move faster if we had more resources," Varmus added, but he pledged to make the best use of the money and people at NCI's disposal.

ASCO President George Sledge spoke of the promise and challenges of the genomics era as relates to cancer care. Cancer death rates are down, he said, but clinicians are still facing an aging population with a growing rate of cancers, an increasing problem in the cost of cancer care, and an "abysmally low" rate of success in Phase III trials for new cancer drugs. The current era of targeted cancer therapy is still going strong, Sledge said, but that fact that sequencing is getting faster and less expensive will soon lead to large-scale sequencing to explain causes of drug resistance, find new treatment targets, and understand the biological basis of cancer. We are on the brink of personalized genomics, Sledge added, which will make it easier to treat cancer, but will also make things more complicated as we begin to reach a greater understanding of the complexities of tumor biology.

In a separate session, Washington University in St. Louis researcher Elaine Mardis tried to introduce the audience of oncologists to some of this new genomic technology — whole-genome sequencing. Whole-genome sequencing presents researchers and clinicians with the full spectrum of somatic genomic mutations needed for a full understanding of tumor biology and evolution, Mardis said. The method is now being applied to patients who are at the end stage of their disease or are difficult to diagnose. Whole-genome sequencing can help identify large-scale genomic events that can lead to cancer, like deletions, translocations, mutations, and fusion genes. In 10 days, Mardis and her colleagues were able to sequence the whole genomes of a tumor and normal tissue pair of samples, for a cost of $7,500. It's still an expensive technology, she added, but the price is dropping fast. Such "deep digital sequencing" can detect the prevalence of mutations in a tumor to determine its heterogeneity, and can also be used to track a tumor's progression over time, she said. In the clinical context, whole-genome sequencing can produce results in a clinically-relevant time frame, and the method can be condensed and done more quickly to speed up the production of results. [To read more about Mardis' work on WGS in cancer patients in this month's Q&A in Genome Technology.]

Mardis' colleague Ramaswamy Govindan added that whole-genome sequencing provides clinicians with a "panoramic view" of cancer, and can help researchers find new targets for therapy. He rather tongue-in-cheekily called former US Secretary of Defense Donald Rumsfeld "the greatest geneticist of all time" for his idea of "known knowns" and "known unknowns." We know what we know, Govindan said, and we know what we don't know. Whole-genome sequencing will allow us to not only know what is now unknown, but will also highlight those things that we currently are unaware of, by providing scientists with novel druggable targets, mechanisms of resistance, deeper sub-categorization of cancer subtypes, and insight into tumor biology, he added.