Multiple mechanisms have been identified that contribute to targeted BRAF treatment resistance including: (i) genetic mutations in growth promoting components such as NRAS or MEK that reactivate the MAPK pathway3,4, as well as hyperactivation of the PI3K/AKT pathway5,6; (ii) alternative splicing of the BRAF gene that promotes RAF-dimerization and downstream signaling in the presence of drug7; (iii) tumor microenvironment changes such hypoxia or increased secretion of growth factors could desensitize melanoma cells from BRAF inhibitors8–11. The gene discussed is BRAF; the disease is neoplasm.