Differently from other ERBB family members, HER2 is considered an orphan receptor since it does not bind directly to EGF-like ligands and activation results from heterodimerization, with ligand-activated EGFR or ERBB3, or from homodimerization in the case of high concentrations of the receptor (such as when overexpressed in cancer cells) [16,17]. This evidence concerns the gene EGFR and cancer.