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

The **HER2–HER3 dimer** is a heterodimeric complex formed by two members of the human epidermal growth factor receptor family—**Human epidermal growth factor receptor 2 (HER2/ErbB2)** and **Human epidermal growth factor receptor 3 (HER3/ErbB3)**. This complex plays a central role in driving potent proliferative and survival signals within cells, especially in cancers such as breast cancer where these receptors are overexpressed or mutated. The formation of this heterodimer results in unusually high rates of tyrosine phosphorylation and robust activation of downstream effectors involved in cell proliferation. Within the asymmetric active conformation, **the kinase domain of HER3 acts as an activator**, while **the kinase domain of HER2 functions as a receiver**, leading to strong signal transduction even though the intrinsic kinase activity of HER3 is impaired. The dynamic nature and high catalytic rate make this dimer particularly effective at promoting oncogenic signaling. Therapeutically, targeting this interaction has been highly successful; monoclonal antibodies such as trastuzumab and pertuzumab disrupt its formation or function, leading to clinical benefit for patients with cancers driven by these pathways. However, resistance can develop through mutations that enhance signaling through this axis or alter drug binding. The presence and activity level of the **HER2–HER3 dimer** serve both as biomarkers for patient selection for anti-HER therapies and potential indicators for monitoring therapeutic efficacy.[1][5]

Other names

HER2-HER3 heterodimerErbB2-ErbB3 dimerHER2/ErbB2–HER3/ErbB3 complex

Inhibition of ligand-induced or constitutive dimerization, blocking downstream proliferative signaling pathways[1][3]