HER2, EGFR

HER2 and EGFR are distinct but functionally related receptor tyrosine kinases of the ErbB family, crucial in cell signaling and cancer. While they can form functional heterodimers, particularly important in cancer signaling as this increases signaling diversity and oncogenic potential, it is incorrect to treat 'HER2, EGFR' as a single molecular entity. EGFR (Epidermal growth factor receptor) is a transmembrane glycoprotein that binds various ligands such as EGF and TGF-α, leading to dimerization (homodimerization or heterodimerization) and activation of intracellular kinase domains, driving cell proliferation, survival, and differentiation. HER2 (Human epidermal growth factor receptor-2), also a transmembrane receptor tyrosine kinase, does not have a known direct ligand but is constitutively in an open conformation, allowing efficient dimerization—especially with ligand-activated EGFR or HER3. Both are independently overexpressed or mutated in numerous cancers and serve as important therapeutic targets, with therapies disrupting their individual functions or their oncogenic heterodimeric interactions.

Drugs target individual components (EGFR or HER2) via kinase inhibition (including ATP binding site inhibition), antibody-mediated blockade of ligand binding or dimerization, antibody-dependent cell-mediated cytotoxicity (ADCC), or as antibody-drug conjugates.