UCLA scientists uncover mechanism for melanoma drug resistance

UCLA researchers have uncovered how an advanced form of melanoma gets around an inhibitor, Zelboraf, which targets the BRAF gene, a gene that is mutated in some metastatic melanoma. In some patients with BRAF-mutated metastatic melanoma, the mutated BRAF gene becomes amplified as the cancer develops resistance to Zelboraf. By increasing the copies of the mutated BRAF gene, the melanoma is trying to over-produce the protein targeted by the drug and, essentially, outnumber the inhibitor. The team examined samples of 20 patients for this study, taking their normal tissue, their tumor tissue before treatment with Zelboraf and a sample when the cancer had responded earlier but subsequently became resistant. The study resulted in five of the 20 patients showing increased copies of the mutated BRAF gene. Cell lines developed from melanoma patients also showed pathways downstream of the amplified gene that could be blocked with inhibitors to fight resistance.