This past summer saw a revolution in therapy against melanoma, the deadliest, most aggressive form of cancer. Patients whose melanoma lesions contain a mutation in the BRAF gene were successfully treated with a BRAF-specific inhibitor, PLX4032. Reports of the drug trial described shrinking tumors and improved health. Yet seven months after therapy began the tumors returned and resumed growing. Now, scientists at The Wistar Institute’s Melanoma Research Center, who were involved in the very early stages of BRAF research that
preceded the drug trial, explain why: the tumor learns to signal around the blocked gene by adjusting its molecular wiring. They also have found a way to overcome resistance by simultaneously targeting multiple signaling pathways, hitting melanoma with a barrage from which it cannot recover.
“The evidence suggests that targeting mutant BRAF can kill cancer cells, but it is not enough by itself to finish off melanoma,” said Meenhard Herlyn, D.V.M., D.Sc. “The good news is that drugs are being developed to work in combination with BRAF inhibitors, which our data clearly shows is our best option if we intend to beat advanced melanoma.”