Progression of RAS-Mutant Leukemia during RAF Inhibitor Treatment

Approximately 50% of patients with metastatic melanoma harbor a somatic V600E mutation ? or, less frequently, a V600K mutation ? in the BRAF kinase.1?4 These activating mutations drive increased ERK signaling, promoting the proliferation and survival of melanoma cells.5 Selective RAF inhibitors, such as vemurafenib and dabrafenib, inhibit ERK signaling and arrest growth in tumors with BRAF V600E or BRAF V600K mutations.3,6?8 Treatment with vemurafenib or dabrafenib induces tumor regression in more than half of patients with BRAF V600E?mutant metastatic melanoma. Both drugs also improve the rate of progression-free survival, as compared with dacarbazine.7,9?11 Vemurafenib . . .