A Promising Target for BRAF/MEK Inhibitor–Resistant Melanoma

Two major unaddressed clinical needs in melanoma are treatment options for BRAF/MEK inhibitor–resistant melanoma and NRAS-mutant melanoma. Resistance to BRAF and MEK inhibitors typically occurs within 6 to 10 months after initiation of therapy. Resistance often occurs with activation of growth factor receptors, which reactivate the MEK/ERK pathway in part through the activation of SRC-family kinases (SFKs).

Researchers have now identified two new investigational RAF inhibitors, CCT196969 and CCT241161, which bind the inactive form of BRAF^V600E. They inhibited not only BRAF-mutant melanoma cells but also treatment-naive RAS-mutant cancer cells and patient-derived melanoma xenografts that had acquired resistance to BRAF and MEK inhibitors, inc…