EGFR, also known as ERBB1 and HER1, is a transmembrane tyrosine kinase receptor (RTK). EGFR is a member of the human epidermal receptor (HER) family and a crucial component of cell signal pathways. Binding with ligands (EGF and TGF-α) leads to conformational changes in EGFR and homodimerization or heterodimerization with other HER family members. There is subsequent autophosphorylation of the cytoplasmic tyrosine kinase (TK) domain with the help of adapter proteins (e.g., SHC and GRB-2), which triggers downstream signaling. There are three main downstream pathways: (1) rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase (MAPK) pathway; (2) phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway and (3) janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway, which stimulates mitosis, leading to cell proliferation and inhibition of apoptosis1. These pathways are crucial in normal cell growth. EGFR also serves as a stimulus for cancer growth. EGFR gene mutations and protein overexpression, both of which activate downstream pathways, are associated with cancers, especially lung cancer. The importance of EGFR to lung cancers supports the concept of ‘oncogene addiction’. Tyrosine kinase inhibitors (TKIs) have been used to treat the cancer harboring EGFR mutations or aberrant activation of EGFR.

References

1.Huang L,et al. Acta Pharm Sin B. 2015;5(5):390–401.