Human epidermal growth factor receptor 2 and Human epidermal growth factor receptor 3 (HER2 and HER3)

The Human Epidermal Growth Factor Receptor 2 (**HER2**) and **HER3** are members of the receptor tyrosine kinase family known as the HER/ErbB family. HER2 (ErbB2) is unique in lacking direct ligand binding but is constitutively active for dimerization, while HER3 (ErbB3) is characterized by impaired tyrosine kinase activity but has multiple sites for downstream signaling. HER2 and HER3 form a potent heterodimer complex upon ligand (such as neuregulin-1β) binding to HER3, leading to strong activation of oncogenic signaling cascades, especially the PI-3K/Akt pathway. This heterodimer is a key driver in the pathogenesis of HER2-amplified cancers, particularly breast cancer, and is the primary target of several therapies, including monoclonal antibodies and kinase inhibitors. Aberrant signaling through this dimer promotes cell proliferation, survival, and therapy resistance, establishing HER2-HER3 as critical and therapeutically actionable targets in oncology[1][2][3][4][5][6][7]. Note on correctness: The entry "HER2 and HER3" refers to a *protein complex* (the HER2/HER3 heterodimer), not a single molecule, and both have distinct canonical forms ("Human epidermal growth factor receptor 2" and "Human epidermal growth factor receptor 3"). For structured databases, each receptor should preferably be entered under its own unified canonical form, but the functional unit of clinical and pharmacological interest—especially in cancer—is the HER2/HER3 dimer[1][4][6].

Other names

HER2 (ErbB2; ERBB2)HER3 (ErbB3; ERBB3)Receptor tyrosine-protein kinase erbB-2Receptor tyrosine-protein kinase erbB-3Neu (rodent homolog of HER2)c-erbB-2c-erbB-3

Inhibition of receptor dimerization (e.g., pertuzumab); Inhibition of receptor tyrosine kinase activity (e.g., lapatinib, neratinib); Antibody-dependent cellular cytotoxicity (e.g., trastuzumab); Targeting downstream signaling (e.g., PI-3K/Akt)