A recent collaborative study by the Harvard-affiliated Dana-Farber Cancer Institute and the Broad Institute of Harvard and MIT has provided researchers with key insight into how particular forms of melanoma—the most deadly form of skin cancer—can become resistant to certain cancer drugs.

In identifying why B-RAF mutant melanoma tumors, a type of tumor with a mutation in the B-RAF enzyme, become resistant to current medications, the researchers may have opened the door to drugs that could potentially prevent relapse.

The team identified a particular enzyme naturally existing in the body, called COT, that can cause cell proliferation even after drug treatment, said Levi A. Garraway ’90, an assistant professor at Harvard Medical School and a co-author of the study.

In a cancerous B-RAF mutant melanoma cell, the traditional drug treatment—a B-RAF inhibitor—would force the cancer into remission. But COT, unaffected by the currently-used drugs, can cause a relapse of the cancer.

“The cancer cells that we were working with have a growth light switch in the on position and when you put the drug in, it turns it off,” said Cory M. Johannessen, a researcher at the Broad Institute and a co-author of the study. “But these cells gain resistance to the drugs and COT turns that switch back on,” he added.

Up to this point, said Johannessen, COT’s functional role in human cancers has been relatively unknown.

But the recent study sheds new light on the function of COT in cancer relapse and allows scientists to look beyond the B-RAF enzyme to find another mechanism to stop the proliferation of cancerous cells.

“There is no reason in principle, that one could not design a COT [enzyme] inhibitor. But the ones that are available this far are not very potent. ” Garraway said. “There are some cases where we understand the biology really well but we have no good drug to hit that biology.”

Cancer relapse has proven a major obstacle in discovering cures for most cancers.

Keith T. Flaherty, a lecturer at Harvard Medical School, said researchers must continuously find drugs to target cancerous cells that have developed resistance to previous medications. He said the process is sometimes described as “whack-a-mole.”

The study was published in the November 25 issue of the journal Nature.