The second study identified that the gene encoding COT/TpI2 called MAP3K8 is a MAPK pathway activator and maybe responsible for the evolution of resistance to vemurafenib in some cases of V600E mutated melanoma [63] Furthermore it subverts RAF signaling by activating ERK signaling by mechanisms downstream of BRAF that are not RAF dependent. The gene discussed is RAF1; the disease is melanoma.