Reactivation of the MAPK pathway is present in 70% of patients who progress on TT,20 achieved through either upregulation or activating mutations of positive regulators of the MAPK pathway (BRAF, MEK1, MEK2 and NRAS) or downregulation of negative regulators such as NF1,31, 32 ultimately driving melanoma proliferation and survival. The gene discussed is BRAF; the disease is melanoma.