HER3 belongs to the human epidermal growth factor receptor (HER) family which also includes HER1/EGFR/erbB1, HER2/erbB2, and HER4/erbB4. As a unique member of the HER family, HER3 lacks or has little intrinsic tyrosine kinase activity. It frequently co-expresses and forms heterodimers with other receptor tyrosine kinases (RTKs) in cancer cells to activate oncogenic signaling, especially the PI-3K/Akt pathway and Src kinase. Elevated expression of HER3 has been observed in a wide variety of human cancers and associates with a worse survival in cancer patients with solid tumors. Studies on the underlying mechanism implicate HER3 expression as a major cause of treatment failure in cancer therapy. Activation of HER3 signaling has also been shown to promote cancer metastasis. These data strongly support the notion that therapeutic inactivation of HER3 and/or its downstream signaling is required to overcome treatment resistance and improve the outcomes of cancer patients.
Keywords: ADCC, antibody-dependent cell-mediated cytotoxicity; Ab, antibody; Cell signaling; Dimerization; EGFR, epidermal growth factor receptor; EMT, epithelial-mesenchymal transition; FDA, Food and Drug Administration; HER, Human epidermal growth factor receptor; HER3; HRG, heregulin; IGF-1R, insulin-like growth factor-I receptor; MAPK, mitogen-activated protein kinase; MEK, MAPK kinase; NSCLC, non-small cell lung cancer; OS, overall survival; PI-3K, phosphoinositide 3-kinase; RTK, receptor tyrosine kinase; TKI, tyrosine kinase inhibitor; Targeted therapy; Therapeutic resistance; Tumor metastasis; lncRNA, long ncRNA; miRNA, microRNA; ncRNA, noncoding RNA.