Practical way to target cancer cell mutations demonstrated

A study led by researchers at Dana-Farber Cancer Institute and Broad Institute of the Massachusetts Institute of Technology and Harvard University provides the first demonstration of a practical method of screening tumors for cancer-related gene abnormalities that might be treated with "targeted" drugs.

The findings, published online Feb. 11 on the Nature Genetics Web site, may help relieve a bottleneck between scientists' expanding knowledge of the genetic mutations associated with cancer and the still-nascent ability of doctors to use that knowledge to benefit patients. The results constitute an important step toward the era of "personalized medicine," in which cancer therapy will be guided by the particular set of genetic mutations within each patient's tumor, the authors suggest.

"It's universally recognized that cancer is a disease of the genome, of mutations within genes responsible for cell growth and survival, and a great deal of effort has gone into finding those mutations, to the point where several hundred to a thousand are now known," said the study's senior author, Levi Garraway, of Dana-Farber and the Broad Institute. "The challenge has been how to determine which of them are involved in each of the hundreds of kinds of cancer that occur in humans - and to develop accurate, affordable methods of detecting key mutations in tumor samples. This study suggests that such a method is feasible on a large scale."

The authors took advantage of a scientific serendipity to devise a simple test to detect important cancer mutations. Mutations in oncogenes (genes linked to cancer) do not occur randomly; rather, they seem to arise most frequently in certain regions of the oncogenes. As a result, researchers didn't necessarily have to scan the entire length of each gene, but could focus instead on the sections most likely to harbor mutations.

Major funding for the study was provided by grants from Genentech, Inc. the American Cancer Society, the National Cancer Institute, the Prostate Cancer Foundation, the Burroughs-Wellcome Fund, the Robert Wood Johnson Foundation, and the Novartis Institute for Biomedical Research.