Despite the success of recent melanoma therapies, advanced cancers eventually evolve resistance to drugs. Researchers report on the mechanics by which melanoma can evolve resistance to a powerful combination of drugs — BRAF and MEK inhibitors. Their studies also uncovered a new potential target for melanoma therapy, a protein called S6K. Additionally, early studies in a laboratory model for melanoma show that a triple combination of drug inhibitors halted the growth of resistant tumors.