The collaboration between the Wellcome Trust Sanger Institute and the Massachusetts General Cancer Center to study the role of genetics in response to cancer treatment is beginning to show results. The study, which began in 2008, released its initial data set, detailing the responses of 350 cancer cell lines to 18 therapeutics. From this, researchers were able to confirm that melanomas with a mutation in the BRAF gene were sensitive to the Astra-Zeneca drug AZ628.
For this first set, Andy Futreal, co-director of the project at Sanger says that the researchers "were interested in really putting the entire platform through its paces, so there was a component of testing compounds which had previously [shown] activity in the context of certain mutations." From this, not only did they confirm that the BRAF mutation in melanoma made it susceptible to AZ628, the team also saw that lines with EGFR mutations were sensitive to EGFR inhibitors and lines with MET gene amplification were sensitive to MET kinase inhibitors. "I think this ability to take apart contextual effects is going to be very important for really taking apart genome-driven drug sensitivities to these targeted agents," Futreal says.
Next, the team will be ramping up the screening effort to a full 1,000 cell lines, all commercially available, and will be testing them against even more drugs, both approved and experimental. In addition, Futreal says they'll be able to ask questions about genetic context, particularly the role of copy number variation and expression in therapeutic response.
All this, the researchers say, should enhance cancer treatment. "We know cancer is a genetic disease. ... Knowing what these cancer genes are allows us to ask the question 'does the presence of one or more of them affect response to the therapeutics being developed, many of which are targeted either at the cancer genes themselves or at the pathways they are active in?'" Futreal says. "This is a fundamental step in getting the best drug in the most sensitive cancer — hopefully improving treatment response for patients."