It's personal now: Alexis Borisy (left) and Michael Pellini lead an effort to make DNA data available to help cancer patients. Credit: Christopher Harting <\/p>\n
Michael Pellini fires up his computer and opens a report on a patient with a tumor of the salivary gland. The patient had surgery, but the cancer recurred. That's when a biopsy was sent to Foundation Medicine, the company that Pellini runs, for a detailed DNA study. Foundation deciphered some 200 genes with a known link to cancer and found what he calls \"actionable\" mutations in three of them. That is, each genetic defect is the target of anticancer drugs undergoing testingthough not for salivary tumors. Should the patient take one of them? \"Without the DNA, no one would have thought to try these drugs,\" says Pellini. <\/p>\n
Starting this spring, for about $5,000, any oncologist will be able to ship a sliver of tumor in a bar-coded package to Foundation's lab. Foundation will extract the DNA, sequence scores of cancer genes, and prepare a report to steer doctors and patients toward drugs, most still in early testing, that are known to target the cellular defects caused by the DNA errors the analysis turns up. Pellini says that about 70 percent of cases studied to date have yielded information that a doctor could act onwhether by prescribing a particular drug, stopping treatment with another, or enrolling the patient in a clinical trial. <\/p>\n
The idea of personalized medicine tailored to an individual's genes isn't new. In fact, several of the key figures behind Foundation have been pursuing the idea for over a decade, with mixed success. \"There is still a lot to prove,\" agrees Pellini, who says that Foundation is working with several medical centers to expand the evidence that DNA information can broadly guide cancer treatment. <\/p>\n
Foundation's business model hinges on the convergence of three recent developments: a steep drop in the cost of decoding DNA, much new data about the genetics of cancer, and a growing effort by pharmaceutical companies to develop drugs that combat the specific DNA defects that prompt cells to become cancerous. Last year, two of the 10 cancer drugs approved by the U.S. Food and Drug Administration came with a companion DNA test (previously, only one drug had required such a test). So, for instance, doctors who want to prescribe Zelboraf, Roche's treatment for advanced skin cancer, first test the patient for the BRAFV 600E mutation, which is found in about half of all cases. <\/p>\n
About a third of the 900 cancer drugs currently in clinical trials could eventually come to market with a DNA or other molecular test attached, according to drug benefits manager Medco. Foundation thinks it makes sense to look at all relevant genes at oncewhat it calls a \"pan-cancer\" test. By accurately decoding cancer genes, Foundation says, it uncovers not only the most commonly seen mutations but also rare ones that might give doctors additional clues. \"You can see how it will get very expensive, if not impossible, to test for each individual marker separately,\" Foundation Medicine's COO, Kevin Krenitsky, says. A more complete study \"switches on all the lights in the room.\" <\/p>\n
So far, most of Foundation's business is coming from five drug companies seeking genetic explanations for why their cancer drugs work spectacularly in some patients but not at all in others. The industry has recognized that drugs targeted to subsets of patients cost less to develop, can get FDA approval faster, and can be sold for higher prices than traditional medications. \"Our portfolio is full of targets where we're developing tests based on the biology of disease,\" says Nicholas Dracopoli, vice president for oncology biomarkers at Janssen R&D, which is among the companies that send samples to Foundation. \"If a pathway isn't activated, you get no clinical benefit by inhibiting it. We have to know which pathway is driving the dissemination of the disease.\" <\/p>\n
Cancer is the most important testing ground for the idea of targeted drugs. Worldwide spending on cancer drugs is expected to reach $80 billion this yearmore than is spent on any other type of medicine. But \"the average cancer drug only works about 25 percent of the time,\" says Randy Scott, executive chairman of the molecular diagnostics company Genomic Health, which sells a test that examines 16 breast-cancer genes. \"That means as a society we're spending $60 billion on drugs that don't work.\" <\/p>\n
Analyzing tumor DNA is also important because research over the past decade or so has demonstrated that different types of tumors can have genetic features in common, making them treatable with the same drugs. Consider Herceptin, the first cancer drug approved for use with a DNA test to determine who should receive it (there is also a protein-based test). The FDA cleared it in 1998 to target breast cancers that overexpress the HER2 gene, a change that drives the cancer cells to multiply. The same mutation has been found in gastric, ovarian, and other cancersand indeed, in 2010 the drug was approved to treat gastric cancer. \"We've always seen breast cancer as breast cancer. What if a breast cancer is actually like a gastric cancer and they both have the same genetic changes?\" asks Jennifer Obel, an oncologist in Chicago who has used the Foundation test. <\/p>\n
The science underlying Foundation Medicine had its roots in a 2007 paper published by Levi Garraway and Matthew Meyerson, cancer researchers at the Broad Institute, in Cambridge, Massachusetts. They came up with a speedy way to find 238 DNA mutations then known to make cells cancerous. At the time, DNA sequencing was still too expensive for a consumer testbut, Garraway says, \"we realized it would be possible to generate a high-yield set of information for a reasonable cost.\" He and Meyerson began talking with Broad director Eric Lander about how to get that information into the hands of oncologists. <\/p>\n<\/p>\n
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Foundation Medicine: Personalizing Cancer Drugs<\/a><\/p>\n","protected":false},"excerpt":{"rendered":" It's personal now: Alexis Borisy (left) and Michael Pellini lead an effort to make DNA data available to help cancer patients. Credit: Christopher Harting Michael Pellini fires up his computer and opens a report on a patient with a tumor of the salivary gland. Continue reading