Pinpointing new targets for cancer treatments is as difficult as finding a needle in a haystack, yet a University of Rochester team has discovered an entire novel class of genes they believe will lead to a greater understanding of cancer cell function and the next generation of effective and less harmful therapies for patients.
In a paper in the journal Nature, available online May 25, the researchers describe how multiple cancer genes cooperate to cause malignant cell transformation. Further, they describe the discovery of approximately 100 genes that work downstream of known cancer-causing mutations, providing a host of new opportunities for intervention.
"We believe that we have found a cornerstone for development of new treatments that ultimately will allow selection of drugs and drug combinations from a pool of compounds directed against these new genes," said lead author Hartmut Land, Ph.D., professor and chair of the Department of Biomedical Genetics at the University of Rochester Medical Center and scientific director of the James P. Wilmot Cancer Center at the URMC.
"However, much more work needs to be done to explore how our findings may lead to successful targeting of various cancer types and cancer stem cells," he said.
Targeted cancer therapy - such as the drug Gleevec that works for patients with certain types of leukemia and gastrointestinal tumors - is based on a keen understanding of the architecture of cancer. Much has been learned in the past several years, but what has been lacking is a clear roadmap leading to dozens of new molecular targets.
Twenty-five years ago Land was among the first scientists to discover that malignant cell transformation required multiple mutations in distinct cancer genes. Ever since, he has been studying the cooperative nature of this process and the inner workings of cancer cell function.
His research group began testing, at the genomic scale, a prediction that genes responding synergistically to cooperating oncogenic mutations might act as the "drivers" toward malignancy, Land said. It now appears that this hunch has paid off.