Human epidermal growth factor receptor 2 (HER2) – Human epidermal growth factor receptor 3 (HER3) heterodimer (HER2-HER3)

The Human epidermal growth factor receptor 2 (HER2) – Human epidermal growth factor receptor 3 (HER3) heterodimer is a potent oncogenic signaling unit within the ErbB family of receptor tyrosine kinases [PMC, 2015; PMC, 2014]. While HER2 lacks a known ligand and HER3 has impaired intrinsic kinase activity, their heterodimerization creates the most active signaling complex in the family [PubMed, 2005; PMC, 2014]. HER3 serves as a critical scaffold, containing six docking sites for the p85 subunit of phosphoinositide 3-kinase (PI3K), which leads to robust activation of the PI3K/Akt/mTOR pathway [PMC, 2015; PMC, 2009]. This pathway is a primary driver of cell survival, proliferation, and resistance to various cancer therapies [PMC, 2014; Clin Cancer Res, 2014]. The HER2-HER3 heterodimer is frequently overexpressed in breast, gastric, and lung cancers, where it correlates with poor prognosis [ResearchGate, 2017; PMC, 2023]. Therapeutic targeting involves agents like pertuzumab, which specifically inhibits the dimerization interface, and bispecific antibodies like zenocutuzumab that target both receptors to prevent signaling [Clin Cancer Res, 2014; PMC, 2024].

Other names

ErbB2-ErbB3 heterodimerHER2-HER3 heterodimerHER2:HER3 complexErbB2:ErbB3 complex

Inhibition of dimerization, ligand blocking, kinase inhibition, and antibody-dependent cellular cytotoxicity (ADCC) [Clin Cancer Res, 2014; PMC, 2022].