BRAF/MEK Dual-Targeted Therapy in Advanced Melanoma

Source: OncLive, June 2019


Ryan J. Sullivan, MD: Inhibiting BRAF-mutated melanoma typically is—we use 2 drugs. We use an inhibitor BRAF itself, targeting the oncogene specifically, and then we inhibit a downstream protein called MEK.

These drugs actually were developed individually. So BRAF inhibitors and MEK inhibitors were developed essentially on separate paths. The first BRAF inhibitors to get into patients were actually RAF inhibitors generally, and they tended not to have specificity for BRAF or the mutated BRAF and weren’t particularly effective. These drugs go by the names of sorafenib, which is actually FDA approved for kidney cancer and hepatocellular carcinoma, and a drug called RAF265, which was tested for melanoma.

Moving on from that, the development of more specific BRAF inhibitors occurred, and the first of those drugs to get into humans was a drug called vemurafenib. Vemurafenib is a highly potent and specific inhibitor of both the normal and the wild type—I’m sorry, the normal and the mutated version of BRAF. And the importance of that is that the adverse effects are actually related to inhibiting BRAF.

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