BRAF and melanoma: The primary clinical mechanism of acquired melanoma resistance to PLX4032 and other BRAF inhibitors (BRAFi) is the reactivation of MAPK pathway signaling which consequently leads to activation of dysregulated proliferation, aberrant cell cycle progression, and resistance to apoptosis (Lito et al., 2012; Rizos et al., 2014; Van Allen et al., 2014).