Melanoma Becomes Resistant to New Combination Therapy Through Genetic Changes

Researchers discover how cancer resists BRAF+MEK inhibitors.

Melanoma develops resistance to a promising new combination drug therapy through unique genetic changes, the results of a recent study indicate.

In a study published online January 15, 2015 in Cancer Cell, researchers evaluated 43 tumor samples from 15 patients prior to treatment with the BRAF+MEK inhibitor combination therapy and after a relapse caused by the melanoma developing resistance to the drugs.

All of the patients in the study initially experienced tumor shrinkage from the therapy before experiencing a relapse.

Genetic material extracted from each biopsied tumor was extensively analyzed, which offered leads into how melanoma cells grown in the laboratory altered growth circuitry to get around the combination therapy.

The researchers discovered that melanoma cells develop “highly unusual genetic changes” in specific key cancer genes, which alerts investigators to the presence of drug resistant melanoma cells. The process also provides clues into potential new methods to overcome this resistance.

"We need to find ways to go beyond the BRAF+MEK drug combination, by possibly finding a third drug, or alter how we prescribe the combo of drugs," said study lead Roger Lo, MD, in a press release. "The idea is to eventual suppress melanoma drug resistance even before it arises."

The discovery of the mechanism in which melanoma cells become resistant to therapy may pave the way for future treatments.

"If we understand how a disease fights your therapy, then we can start to design more effective treatment strategies," Dr. Lo said.