Molecular Targeting Therapy against EGFR Family in Breast Cancer: Progress and Future Potentials

Abstract

The epidermal growth factor receptor (EGFR) family contains four transmembrane tyrosine kinases (EGFR1/ErbB1, Her2/ErbB2, Her3/ErbB3 and Her4/ErbB4) and 13 secreted polypeptide ligands. EGFRs are overexpressed in many solid tumors, including breast, pancreas, head-and-neck, prostate, ovarian, renal, colon, and non-small-cell lung cancer. Such overexpression produces strong stimulation of downstream signaling pathways, which induce cell growth, cell differentiation, cell cycle progression, angiogenesis, cell motility and blocking of apoptosis.The high expression and/or functional activation of EGFRs correlates with the pathogenesis and progression of several cancers, which make them attractive targets for both diagnosis and therapy. Several approaches have been developed to target these receptors and/or the EGFR modulated effects in cancer cells. Most approaches include the development of anti-EGFRs antibodies and/or small-molecule EGFR inhibitors. This review presents the state-of-the-art and future prospects of targeting EGFRs to treat breast cancer.

Clinicopathological characteristics and genetic analysis of pulmonary carcinoid tumors: A single‑center retrospective cohort study and literature review

“…In the present study, four genes were revealed to be mutated at a high frequency, including KIT, ERBB4, MET and IGF1R, which were mutated in 33.3% patients. These genes encode typical tyrosine-protein kinases or receptor tyrosine kinases that are cell surface receptors for multiple signaling pathways and serve an essential role in the regulation of cell survival, proliferation and apoptosis (42)(43)(44)(45). Mutations in these genes are important therapeutic targets of molecular targeted therapeutic drugs, such as the TKIs imatinib and sunitinib (42)(43)(44)(45).…”

Praeruptorin B Mitigates the Metastatic Ability of Human Renal Carcinoma Cells through Targeting CTSC and CTSV Expression

“…EGFR, also called ErbB1 or HER1, is a member of the ErbB family of receptors, which are transmembrane glycoproteins that stimulate their corresponding signaling pathway, including the KRAS-MEK1/2-ERK1/2 pathway, phosphoinositide 3-kinase (PI3K)-AKT kinase pathway, and STAT signaling pathway [36,37]. Evidence is accumulating for a critical role played by the EGFR-mediated signaling pathway in cell proliferation, survival, angiogenesis, and cancer metastasis [38].…”

Identification of New Key Genes in Breast Cancer by Co-expression Network Analysis

“…ERBB2, commonly referred to as HER2, encodes a member of the epidermal growth factor receptor family of receptor tyrosine kinases, it is amplified and/or overexpressed in 20-30% of invasive breast carcinomas [13]. Amplification and/or overexpression of this gene have also been reported in many other cancers including ovarian and gastric cancer [14][15][16]. ERBB2 binds tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signaling pathways, such as PI3K/AKT activation and RET signaling [17].…”