Multiple resistant mechanisms to BRAF inhibitors have been discovered which include epigenetic (hypermethylation of CpG islands), genomic (Hippo effector YAP, BRAF splice variants, BRAF gene amplification, mutations in RAS-RAF-MEK-ERK pathway) and phenotypic (tumor heterogeneity and plasticity) [23, 24]. Here, BRAF is linked to neoplasm.