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The fourth member of the HER family, hit by the irreversible pan-HER inhibitors afatinib, dacomitinib and neratinib along with EGFR and HER2. It has no approved drug of its own, and its role in cancer is less clear than that of its siblings.
ERBB4 (HER4) is a receptor tyrosine kinase activated by neuregulins that pairs with HER2 and other family members. Unlike EGFR and HER2 it is not an established oncogenic driver, and some studies link its expression to better outcomes in breast cancer. The irreversible pan-HER inhibitors afatinib and dacomitinib, approved for EGFR-mutant lung cancer, and neratinib, approved for HER2-positive breast cancer, inhibit ERBB4 as part of covering the whole family and preventing escape through HER2 or HER3 dimers. Rare ERBB4 mutations occur in melanoma and lung cancer but have no approved matched therapy.
In plain words · The fourth member of the HER family, hit by the irreversible pan-HER inhibitors afatinib, dacomitinib and neratinib along with EGFR and HER2. It has no approved drug of its own, and its role in cancer is less clear than that of its siblings.
The fourth member of the HER family, hit by the irreversible pan-HER inhibitors afatinib, dacomitinib and neratinib along with EGFR and HER2. It has no approved drug of its own, and its role in cancer is less clear than that of its siblings.
Neuregulin receptor of the HER family; inhibited by pan-HER covalent inhibitors rather than by a dedicated drug.
No product in this corpus aims at HER4 (ERBB4) yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Tumour-associated overexpression: HPA finds the RNA cancer enhanced in cancer (Breast Invasive Carcinoma (TCGA)) and tissue enhanced in normal blood vessel, brain, fallopian tube, so the tumour and the normal tissue it comes from share the target and the medicine relies on the difference in level. HPA ERBB4: RNA tissue enhanced (blood vessel 8 nTPM, brain 8 nTPM, fallopian tube 11 nTPM); no normal tissue stained high; highest cancer staining pancreatic cancer (1 of 12 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Skin cancer (all types), Lung cancer (all types), Breast cancer (all types)); Open Targets associates it with 3 specific cancer types at or above 0.5 (non-small cell lung carcinoma, breast cancer, medullary thyroid gland carcinoma). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas ERBB4 tissue; Human Protein Atlas ERBB4 pathology; Open Targets ENSG00000178568 associations
First described 1993. Earliest sequence paper UniProt cites for the protein: Plowman G.D. et al, Proc. Natl. Acad. Sci. U.S.A, 1993, "Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family". Source.
Neuregulin receptor of the HER family; inhibited by pan-HER covalent inhibitors rather than by a dedicated drug.
RNA: tissue enhanced (blood vessel 8 nTPM, brain 8 nTPM, fallopian tube 11 nTPM), detected in many normal tissues.
No normal tissue stained high; medium in Adipose tissue, Appendix, Bone marrow, Breast, Cervix, Colon and more.
RNA cancer enhanced: Breast Invasive Carcinoma 7 pTPM.
Medium only: breast cancer, cervical cancer, colorectal cancer, endometrial cancer.
HPA ERBB4 tissue · HPA ERBB4 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"HER4" OR ABSTRACT:"HER4" OR TITLE:"ERBB4" OR ABSTRACT:"ERBB4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about HER4 (ERBB4), not a curated reading list.
Shares Dacomitinib, Afatinib, Non-small-cell lung cancer.
Shares Dacomitinib, Non-small-cell lung cancer.
Shares Afatinib, Non-small-cell lung cancer.
Shares Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2-positive breast cancer.
Shares Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2-positive breast cancer, Non-small-cell lung cancer.
Shares Afatinib, HER2-positive breast cancer, Non-small-cell lung cancer.
Shares Dacomitinib, Non-small-cell lung cancer.
Shares Dacomitinib, Afatinib, Non-small-cell lung cancer.