ERBB3
Overview
ERBB3 (Erb-B2 Receptor Tyrosine Kinase 3), also known as HER3, is a member of the ERBB receptor family. It lacks intrinsic kinase activity and signals primarily as a heterodimer with ERBB2 (HER2). ERBB3 is a target of neratinib (a pan-HER TKI that inhibits ERBB1/2/4 and reduces ERBB3 signaling) and is relevant in cervical cancer as a co-target of ERBB2-directed therapy.
Alterations observed in the corpus
- ERBB3 identified among the recurrently altered genes in cervical cancer profiled by MSK-IMPACT (177 patients); specific frequency not reported in the primary narrative PMID:37643132.
- ERBB3 is part of the progenitor/migratory gene program shared between the postnatal human adrenal gland progenitor hC1 and the high-risk undifferentiated neuroblastoma nC3 cluster; identified as a significantly upregulated marker (FDR <0.01, Welch’s t-test) PMID:34493726.
- Although the ErbB family paper names all four ErbB members in the context of tumour radioresistance, ERBB3 is not experimentally interrogated in the ADC radiosensitization experiments PMID:27698471.
- Identified as a significantly mutated gene in 188 primary LUAD tumours (TSP cohort); receptor tyrosine kinase in the ERBB family. PMID:18948947
- ERBB3 V104M detected in CRC C106-resistant cells at resistance to KRASG12C + EGFR inhibition PMID:36355783
- ERBB3 amplification in 5% of GBC; mutations more frequent in T1/T2 primaries (16% vs 0%) PMID:36228155
- Somatic mutations in 2/65 TNBC cases in a WGS cohort (BCCRC) PMID:22495314
- Somatic mutations detected in TCGA colorectal adenocarcinoma cohort (276 tumors) PMID:22810696
- Mutated in 8% (6/72) of colorectal cancers with multiple hotspot mutations; identified as oncogenic PMID:22895193
- ERBB3 mutated in 11% of muscle-invasive bladder cancers (6% in pathway analysis), flagged as potentially sensitive to ERBB kinase inhibitors in TCGA urothelial carcinoma comprehensive genomic characterization PMID:24476821
- ERBB3 (HER3) is co-targeted with EGFR by the bispecific ADC BL-B01D1 in NPC, achieving 38% ORR in the NPC sub-cohort in platinum-refractory disease. PMID:24952746
- ERBB-pathway member cited in context of prior GBC whole-exome data showing recurrent ERBB-pathway mutations activating AKT in GBC PMID:24997986
- Altered in 15% of gastric adenocarcinoma (STAD) cases (TCGA); mutations enriched in MSI tumours, with 13/16 at COSMIC/recurrent sites PMID:25079317
- V104M extracellular-domain hotspot mutation in 1/22 gynaecologic carcinosarcoma cases; flagged as actionable for ERBB-family inhibitor antibodies in Phase II development PMID:25233892
- Significant association with T stage in UTUC (upper tract urothelial carcinoma) cohort PMID:26278805
- ERBB3 (HER3) mutations were catalogued across cancer types in a large-scale targeted sequencing study PMID:28336552
- ERBB3 alterations were detected in a pan-cancer sequencing cohort as part of the ErbB receptor tyrosine kinase family analysis PMID:28373299
- Oncogenic alterations in 7% of CIN-subtype esophagogastric cancers; listed among potentially targetable kinases PMID:29122777
- 16 patients with somatic ERBB3 (HER3) mutations enrolled in SUMMIT; 11 unique missense mutations clustered in the extracellular furin-like and receptor domains; no RECIST responses to neratinib monotherapy; frequently co-occurred with ERBB2 mutations in non-responders PMID:29420467
Cancer types (linked)
- CESC — identified as a recurrently altered gene in the MSK cervical cancer cohort PMID:37643132.
- NBL — ERBB3 marks the hC1 postnatal adrenal progenitor and the high-risk undifferentiated nC3 neuroblastoma cluster as part of the shared migratory/progenitor gene signature PMID:34493726.
Co-occurrence and mutual exclusivity
Therapeutic relevance
- Neratinib (pan-HER kinase inhibitor targeting ERBB1, ERBB2, and ERBB4; reduces ERBB3 signaling) showed 25% ORR and 7.0-month median PFS in HER2-mutant cervical cancer PMID:37643132.
Open questions
- None flagged in the corpus.
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:18948947
This page was processed by crosslinker on 2026-05-14. - PMID:36355783
This page was processed by crosslinker on 2026-05-14. - PMID:36228155
This page was processed by crosslinker on 2026-05-14. - PMID:22495314
This page was processed by crosslinker on 2026-05-14. - PMID:22810696
This page was processed by crosslinker on 2026-05-14. - PMID:22895193
This page was processed by crosslinker on 2026-05-14. - PMID:24476821
This page was processed by crosslinker on 2026-05-14. - PMID:24952746
This page was processed by crosslinker on 2026-05-14. - PMID:24997986
This page was processed by crosslinker on 2026-05-14. - PMID:25079317
This page was processed by crosslinker on 2026-05-14. - PMID:25233892
This page was processed by crosslinker on 2026-05-14. - PMID:26278805
This page was processed by crosslinker on 2026-05-14. - PMID:28336552
This page was processed by wiki-cli on 2026-05-14. - PMID:28373299
This page was processed by wiki-cli on 2026-05-14. - PMID:29122777
This page was processed by wiki-cli on 2026-05-15. - PMID:29420467
This page was processed by wiki-cli on 2026-05-15.