Thus, this negative cooperativity provides an explanation for why these drugs are ineffective in tumours expressing non-V600-B-Raf mutants that constitutively self-dimerise (Yao et al, 2015), and for why the dimeric V600E-B-Raf splice variants often mediate acquired drug resistance in melanomas expressing V600E-B-Raf (Poulikakos et al, 2011). Here, BRAF is linked to melanoma.