ERBB2 and cancer: The main mechanisms of resistance to anti-HER2 agents are (1) overabundance of HER ligands and receptors allowing for alternative dimerization that lead downstream pathways to continue to signal despite being partially inhibited [87]; (2) reactivation of pathway signaling through loss of downstream negative-regulators, or gain of activating mutations [79,88,89]; (3) employment of alternative pathways to escape HER2 blockade and to continue drive the growth of cancer cells [90,91].