Using drug combinatorial screening can identify effective combinations for melanomas with genetic variants, including BRAF and RAS mutations that confer either primary or secondary resistance to known therapies. According to a study published in the January issue of Cancer Discovery, the high-throughput drug screening method identified previously unrecognized patterns of drug interaction with the potential for clinical efficacy in treating defined subgroups of melanoma. Such a screening approach may be applicable to other cancers. Using an array of small-molecule inhibitors on early-passage melanoma cultures, the researchers applied a systematic combinatorial high-throughput drug screening (cHTS) approach to evaluate the selectivity of drugs, alone and in pairs, and in the context of BRAF- or RAS-activating mutations (affecting 40 percent and 20 percent of human melanomas, respectively) in the hopes that more defined genotype-selective patterns would yield higher efficacies, thus combatting the problem of limited responses to single agents. “Some patients who have a specific cancer-driving genetic mutation never respond to the matching drug, while nearly all those who initially respond eventually become resistant to the effects of the drug,” says co-author David Stern, Ph.D., from Yale University School of Medicine in New Haven, Conn. “There is a great need for drugs to […]