Human epidermal growth factor receptor 3 (HER3) (HER3)

Human epidermal growth factor receptor 3 (HER3), encoded by the ERBB3 gene, is a member of the ErbB family of receptor tyrosine kinases [1, 3]. It is distinct from other family members due to its lack of significant intrinsic kinase activity, functioning instead as a pseudokinase that must heterodimerize with partners like HER2 or EGFR to initiate signaling [1, 2]. This dimerization leads to the potent activation of the PI3K/Akt/mTOR pathway, which drives cell proliferation, survival, and metabolic regulation [2, 5]. HER3 is frequently overexpressed in various malignancies, including breast, lung, and colorectal cancers, and is a well-documented driver of resistance to therapies targeting other ErbB receptors [2, 4]. Therapeutic strategies currently include monoclonal antibodies that inhibit ligand binding or dimerization, and antibody-drug conjugates (ADCs) like patritumab deruxtecan that leverage HER3 expression for targeted cytotoxic delivery [4, 6]. Sources: [1] UniProt P21860; [2] PMID: 32661054; [3] NCBI Gene 2065; [4] PMID: 30215560; [5] PMID: 24510944; [6] ClinicalTrials.gov NCT04619004.

Other names

ERBB3Receptor tyrosine-protein kinase erbB-3ErbB-3LCCS2MDA-BF-1p185-erbB3p45-sErbB3p85-sErbB3

HER3-targeted therapies primarily function by blocking the binding of its ligand, neuregulin-1 (NRG1), or by preventing its heterodimerization with other ErbB family members like HER2 and EGFR, thereby inhibiting the downstream PI3K/Akt signaling pathway. Additionally, antibody-drug conjugates (ADCs) utilize HER3 as a cell-surface anchor to internalize and deliver potent cytotoxic agents directly into the tumor cell, while bispecific antibodies may target HER3 alongside other receptors to overcome resistance mechanisms.