ERBB3 and neoplasm: Among most, well-studied non-genetic mechanisms of resistance in melanoma are as follows: (a) autocrine activation of receptor tyrosine kinases such as ERBB3 which drives pAKT-dependent cell survival and proliferation [10, 11]; (b) enhanced mitochondrial biogenesis and aberrant bioenergetics, which makes the tumor increasingly dependent upon oxidative phosphorylation and HSP90 activity[7]; (c) drug induced changes in the immune and inflammatory niches that increase drug tolerance to MAPK inhibitors [22, 40].