Epidermal growth factor receptor family (EGFR family)

The Epidermal growth factor receptor family (EGFR family) is a subclass of receptor tyrosine kinase (RTK) proteins consisting of four members: EGFR (HER1), HER2, HER3, and HER4. They are crucial for various cellular processes including proliferation, differentiation, and development. EGFR, a 170 kD protein, features extracellular ligand-binding and cysteine-rich domains, a transmembrane region, and an intracellular tyrosine kinase domain. Upon ligand binding (such as EGF, TGF-α, HB-EGF) and dimerization (homo- or hetero-dimers), these receptors activate multiple downstream signaling cascades, including the Ras/Raf/MAPK, PI3K/Akt, PLC-γ, and JNK pathways, which collectively regulate DNA synthesis, proliferation, migration, adhesion, and differentiation. Dysregulation of EGFR family members, often through overexpression, gain of function mutations, or autocrine activation, plays a significant role in cancer development and progression by promoting uncontrolled cell growth, survival, and angiogenesis. Consequently, they are important therapeutic targets in cancer. Targeted therapies include monoclonal antibodies (e.g., trastuzumab, pertuzumab), tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (e.g., ado-trastuzumab emtansine). While these therapies have improved clinical outcomes for various cancers (e.g., breast, NSCLC), treatment can lead to cardiotoxicity, partly due to the cardioprotective role of HER2 signaling.

Other names

EGFRHER familyHER1HER2HER3HER4

Targeting the extracellular ligand-binding domain (antibodies) or the intracellular tyrosine kinase domain (TKIs) to disrupt downstream signaling pathways such as Ras/Raf/MAPK and PI3K/Akt, thereby inhibiting cell proliferation, survival, and angiogenesis.