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Not Yet Perfected

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In a profile of Johns Hopkins University's Bert Vogelstein in Science, Jocelyn Kaiser says he and his co-PI Kenneth Kinzler have helped "lay the foundation of cancer genetics," work that now inspires other researchers to use genetics to predict cancer risk and develop personalized treatments. And yet, Kaiser adds, Vogelstein and Kinzler seem to spend most of their time these days being skeptical about these efforts. "Vogelstein seems to enjoy pricking balloons. Recently, he has focused on a new target: exuberance over targeted cancer drugs," Kaiser says.

Vogelstein says his focus on targeted drugs began when he read a paper on a patient with melanoma who developed resistance to BRAF inhibitors only five months after the treatment wiped out all his tumors. To investigate resistance, Kaiser says, researchers in the Vogelstein-Kinzler lab are using a "liquid biopsy" technique, where they draw blood samples from patients and then analyze the sample to find tumor DNA. "With Harvard University computational biologist Martin Nowak, they devised a model showing that even before the patient begins treatment, some tumor cells always carry genes with random mutations that can support resistance to targeted drugs," Kaiser says. This form of resistance, they wrote last month in Nature, is therefore 'a fait accompli.'"

At In the Pipeline, Derek Lowe says there are many labs using the liquid biopsy idea, but as with any screening method, the worry here is the rate of false positives. "As you make finer and finer distinctions among different tumor types, the incidence of any given one in the population gets lower and lower, and thus your test has to be more and more reliable in order to avoid overdiagnosing hordes of panicked patients," he says. If liquid biopsy works as a testing method, it would be a great advance for patients, he adds. But a less-than-perfect test would be worse than not having one at all.

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