The compounds to be screened in the Mass General/Wellcome study include both traditional chemotherapies, which can affect both healthy and cancerous tissue, and molecularly targeted drugs, designed to attack a particular genetic flaw specific to cancer cells. The researchers are also working with drug companies to test novel compounds that are either in or close to early stage clinical testing. Pharmaceutical companies can use the results to define the genetic profile of patients most likely to respond to the drug. Focusing clinical trials in this manner should speed up the process, and may even allow the approval of drugs that would have failed in the broader population. “I think that’s the big drive for them to come to us,” says Benes.
Initial results of the study, released last week, identified some previously known cancer mutations, such as a gene called BRAF, that affect drug efficacy, confirming that the approach works. Earlier work showed that mutations in this gene affect how well melanoma patients respond to certain drugs. “But we have much more complex analysis going on that shows combinations of mutations that appear to drive response,” says Benes. Researchers are making the data publicly available.
The findings may also aid development of diagnostic tests designed to capture a genetic snapshot of an individual’s tumor. Foundation Medicine, a startup based in Cambridge, MA, is developing one such test. “The objective is to generate diagnostic tests that are comprehensive, consolidating information on particular genetic alterations now associated with drug response and resistance into a single test, so you don’t have to do dozens of tests,” says Garraway, one of the company’s cofounders. “Those who work at Foundation will be keeping eye out on results from these resources to determine whether markers that emerge should be part of such a test.”