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A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.
Human epidermal growth factor receptor 2 is a receptor tyrosine kinase amplified in ~15-20% of breast cancers and a subset of gastric, colorectal, lung (mutations), and biliary cancers. Trastuzumab (1998) was the first targeted antibody in solid tumours. Trastuzumab deruxtecan redefined the target by working in 'HER2-low' tumours that older drugs ignored, and in 2026 gained approval in early-stage disease.
In plain words · A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.
Backbone ribbon from PDB 1N8Z. RCSB PDB 1N8Z. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.
Ligand-less receptor that heterodimerises with HER3/EGFR to drive PI3K and MAPK signalling. Amplification is a true oncogenic driver; low expression is merely a delivery address for ADCs.
44 products aim at HER2: antibodies, antibody-drug conjugates, bispecific antibodies, vaccines, small molecules and other agents. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
Tumour-associated overexpression or amplification: 7 of 8 label readouts filed under it score protein level or gene copies (HER2 IHC 0 (HER2-negative, including ultralow), HER2 IHC 1+, HER2 IHC 2+ (equivocal, reflex to ISH), HER2 IHC 3+ (HER2-positive by immunohistochemistry) and more), so the medicines rely on the tumour carrying more of it than normal tissue; 1 measure a variant (HER2 (ERBB2) activating mutation). HPA ERBB2: RNA low tissue specificity; blood lineage group enriched (granulocytes 1 nTPM, T-cells 5 nTPM); no normal tissue stained high; highest cancer staining breast cancer (4 of 11 high). Distribution: 5 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Gastric & gastro-oesophageal junction cancer, Lung cancer (all types), Biliary tract cancer (all types), Colorectal cancer); approvals of single-target medicines aimed at it also list Bladder & urothelial cancer, Salivary gland cancers, Endometrial cancer, Oesophageal cancer and more, not counted; Open Targets associates it with 15 specific cancer types at or above 0.5 (non-small cell lung carcinoma, gastric cancer, breast carcinoma, gastric adenocarcinoma, urinary bladder cancer, lung adenocarcinoma and more). Tissue-agnostic: HER2 IHC 3+ (HER2-positive by immunohistochemistry) threshold "IHC 3+" for Trastuzumab deruxtecan is tissue-agnostic; Trastuzumab deruxtecan US 2024: "HER2 IHC3+ solid tumours (tumour-agnostic)". (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: HER2 IHC 0 (HER2-negative, including ultralow) label threshold; Human Protein Atlas ERBB2 tissue; Human Protein Atlas ERBB2 pathology; Open Targets ENSG00000141736 associations
First described 1985. Earliest sequence paper UniProt cites for the protein: Coussens et al, Science, 1985, "Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Cell lines and mouse models for this target →
Ligand-less receptor that heterodimerises with HER3/EGFR to drive PI3K and MAPK signalling. Amplification is a true oncogenic driver; low expression is merely a delivery address for ADCs.
RNA: low tissue specificity, detected in all normal tissues. Blood: group enriched (granulocytes 1 nTPM, T-cells 5 nTPM).
No normal tissue stained high; medium in Appendix, Breast, Cervix, Endometrium, Fallopian tube, Heart muscle and more.
Medium only: colorectal cancer, endometrial cancer, lung cancer, pancreatic cancer.
HPA ERBB2 tissue · HPA ERBB2 pathology · HPA protein class: CD markers, 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.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| HER2-positive breast cancer | 100% | IHC 3+ or ISH-amplified (defining) | Nature | |
| HR-positive / HER2-negative breast cancer | 55-65% | HER2-low (IHC 1+ or 2+/ISH-) | Nature | |
| Triple-negative breast cancer | 38% | HER2-ultralow (IHC 0 with faint membrane staining in 10% or fewer cells) | 37.6% ultralow, 38.4% null and 24.0% low among 367 non-metastatic TNBCs; ultralow tumours were smaller and lower grade and more often carried BRCA1 promoter methylation, and HER2 category did not affect relapse-free survival over 10.3 years (Boissiere-Michot 2026). | doi.org |
| Triple-negative breast cancer | 30-40% | HER2-low (IHC 1+ or 2+/ISH-) | Nature | |
| Triple-negative breast cancer | 24-37% | HER2-low (IHC 1+ or 2+/ISH-negative) | 36.6% of triple-negative against 65.4% of hormone receptor-positive disease among 3,689 HER2-negative patients (Schettini 2021); 395 of 1,162 hormone receptor-negative tumours, 34.0%, in four German neoadjuvant trials (Denkert 2021); 24.0% of 367 chemotherapy-naive non-metastatic TNBCs (Boissiere-Michot 2026); 63 of 557 DESTINY-Breast04 patients, 11.3%, were hormone receptor-negative (Modi 2022). cBioPortal: IHC 1+ or 2+ recorded for 34 of 166 scored triple-negative samples, 20%, with a further 66 recorded as 0 to 1+ (breast_msk_2018); ERBB2 mutation in 10 of 299, 3.3%, in brca_metabric. | doi.org |
| Gallbladder cancer | 9-31% | Protein overexpression (IHC) | 31.3% HER2-positive among 80 resected Japanese gallbladder carcinomas scored by the gastro-oesophageal guideline (Hiraoka 2020); 12.8% overexpression among 187 Chilean cases scored by ASCO/CAP breast criteria, with 20% equivocal (Roa 2014); 9.4% of 53 Italian gallbladder carcinomas HER2-positive by HERIZON-BTC-01 criteria (Angerilli 2026). | doi.org |
| Gastric & gastro-oesophageal junction cancer | 15-20% | IHC 3+ or 2+/ISH+ | ToGA screening | Wikipedia |
| Biliary tract cancer | 10-20% | IHC 3+ or amplification | Higher in gallbladder/extrahepatic | Wikipedia |
| Gallbladder cancer | 8-10% | Amplification | 8% amplification alone plus 1.5% amplification with a mutation among 260 patients (Mondaca 2024); about 8% of 376 Indian patients (Suryavanshi 2025); high-level amplification in 25 of 244 samples, 10.2%, in cBioPortal gbc_mskcc_2022 and 7 of 103, 6.8%, in gbc_msk_2018. ERBB2 alterations of any kind: 15% (Giraldo 2022), 16% of 85 (Javle 2016), 14% overall and 15% versus 9% in the American and Chilean cohorts (Mondaca 2024). | doi.org |
| Gallbladder cancer | 4-8% | Activating mutation (S310F/Y hotspot) | 4% mutation alone, 1.5% with amplification and 0.4% fusion among 260 patients (Mondaca 2024); S310F/Y hotspot predominance among Indian ERBB2 alterations (Suryavanshi 2025); mutations in 19 of 244 samples, 7.8%, in cBioPortal gbc_mskcc_2022; 9.4% of 32 exomes in gbc_shanghai_2014. | doi.org |
| Colorectal cancer | 4-6% | Activating mutation (not amplification) | cBioPortal: 378 of 7,237, 5.2%, in crc_msk_2026; 53 of 1,134, 4.7%, in crc_msk_2017; 64 of 1,516, 4.2%, in crc_eo_2020; 20 of 534, 3.7%, in coadread_tcga_pan_can_atlas_2018; 38 of 619, 6.1%, in coadread_dfci_2016. ERBB3 mutations were among the recurrent receptor kinase events of the Genentech exome series (Seshagiri 2012). | cBioPortal (TCGA) |
| Colorectal cancer | 3-5% | Amplification/IHC 3+ | RAS wild-type enriched | Wikipedia |
| Pancreatic ductal adenocarcinoma | 1-5% | Amplification (mutation in a further 1%) | cBioPortal high-level amplification: 9 of 183, 4.9%, in paad_tcga_pan_can_atlas_2018; 12 of 109, 11.0%, in paad_utsw_2015; 28 of 2,336, 1.2%, plus 18 mutations in pdac_msk_2024; 4 of 395 in pancreas_msk_2024. Focal amplifications of ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA were found at low individual prevalence in 100 whole genomes (Waddell 2015); ERBB2 amplification in 2.2% of 266 KRAS wild-type tumours (Philip 2022). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 2-4% | Exon 20 insertion and kinase-domain missense | cBioPortal, samples with an exon 20 insertion: 58 of 2,653, 2.2%, in luad_mskcc_2023_met_organotropism; 51 of 2,621, 1.9%, in nsclc_ctdx_msk_2022; 20 of 915, 2.2%, in lung_msk_2017; 8 of 232, 3.4%, in lung_nci_2022; 5 of 302, 1.7%, in luad_oncosg_2020. Any ERBB2 mutation reaches 110 of 2,653 (4.1%) and 103 of 2,621 (3.9%). Y772_A775dup is the dominant allele, 42 of 110 records in luad_mskcc_2023_met_organotropism. The Lung Cancer Mutation Consortium found ERBB2 in 19 of 733, 3% (Kris 2014). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 2-3% | ERBB2 exon 20 mutation | cBioPortal (TCGA) | |
| Colorectal cancer | 2-3% | High-level amplification | cBioPortal high-level amplification: 198 of 7,237, 2.7%, in crc_msk_2026; 35 of 1,134, 3.1%, in crc_msk_2017; 47 of 1,516, 3.1%, in crc_eo_2020; 20 of 592, 3.4%, in coadread_tcga_pan_can_atlas_2018; 8 of 257 in coadread_tcga_pub; 32 of 1,015 in crc_sysucc_2022. ERBB2 amplification was among the potentially drug-targetable recurrent copy-number events named in the TCGA analysis (Cancer Genome Atlas Network 2012). Immunohistochemical overexpression was 2.2% of 1,342 stage IV and 1.3% of 1,914 stage II-III patients, with 27 of 28 stage IV overexpressing cases amplified on fluorescence in situ hybridisation (Richman 2016). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 1-3% | High-level amplification | cBioPortal high-level amplification: 51 of 2,422, 2.1%, in luad_mskcc_2023_met_organotropism; 29 of 915, 3.2%, in lung_msk_2017; 33 of 2,621, 1.3%, in nsclc_ctdx_msk_2022; 9 of 511, 1.8%, in luad_tcga_pan_can_atlas_2018; 12 of 487, 2.5%, in lusc_tcga_pan_can_atlas_2018. | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
A166 is an experimental antibody-drug conjugate from Sichuan Kelun-Biotech Biopharmaceutical in phase 3 trials for HER2-positive breast cancer, aimed at HER2.
ABSK061 is an experimental small-molecule drug from Abbisko Therapeutics in phase 2 trials for gastric & gastro-oesophageal junction cancer, bladder & urothelial cancer and non-small-cell lung cancer, aimed at HER2 and FGFR2.
Afatinib (Gilotrif) is a second-generation pill that binds EGFR, HER2 and HER4 irreversibly, approved in 2013 for EGFR-mutant lung cancer. Its lasting value is activity against the uncommon EGFR mutations G719X, L861Q and S768I, approved in 2018, because osimertinib has displaced it for common mutations and its wild-type EGFR binding causes more rash and diarrhoea.
ARX788 is a HER2 ADC with a precisely placed, non-cleavable payload that beat lapatinib-capecitabine in China and showed activity in brain metastases.
AVZO-021 is an experimental small-molecule drug from Avenzo Therapeutics in phase 2 trials for HR-positive / HER2-negative breast cancer, ovarian cancer and endometrial cancer, aimed at HER2.
Cinrebafusp alfa is an experimental fusion protein from Pieris Pharmaceuticals in phase 2 trials for gastric & gastro-oesophageal junction cancer, aimed at HER2.
Disitamab vedotin is a Chinese HER2 ADC approved for gastric and bladder cancer, now in global trials with Pfizer.
GLSI-100 is an experimental cancer vaccine from Greenwich LifeSciences in phase 3 trials for HR-positive / HER2-negative breast cancer, aimed at HER2.
GQ1005 is an experimental antibody-drug conjugate from GeneQuantum Healthcare (Suzhou) in phase 3 trials for HER2-positive breast cancer, aimed at HER2.
The tests that grade a breast or stomach cancer's HER2 level, from the original trastuzumab test in 1998 to the new 'HER2-low' and 'ultralow' cut-offs.
HLX11 is an experimental monoclonal antibody from Shanghai Henlius Biotech in phase 3 trials for HR-positive / HER2-negative breast cancer and HER2-positive breast cancer, aimed at HER2.
HLX22 is an experimental monoclonal antibody from Shanghai Henlius Biotech in phase 3 trials for gastric & gastro-oesophageal junction cancer and HR-positive / HER2-negative breast cancer, aimed at HER2.
IAH0968 is an experimental small-molecule drug from SUNHO（China）BioPharmaceutical CO. in phase 3 trials for gastric & gastro-oesophageal junction cancer, aimed at HER2.
IBI354 is an experimental antibody-drug conjugate from Innovent Biologics (Suzhou) in phase 3 trials for HER2-positive breast cancer and ovarian cancer, aimed at HER2.
Inetetamab is 3SBio's HER2 antibody, approved in China in 2020 with vinorelbine for HER2-positive metastatic breast cancer.
KN026 is an experimental monoclonal antibody from Shanghai JMT-Bio in phase 3 trials for HER2-positive breast cancer and HR-positive / HER2-negative breast cancer, aimed at HER2.
Lapatinib was the first HER2-blocking pill (2007) and is now mostly a comparator arm and a late-line option, displaced by tucatinib and ADCs.
A trastuzumab look-alike with an engineered tail that binds immune cells more tightly; approved in 2020 but rarely used after ADCs arrived.
A pill taken for a year after trastuzumab to further reduce recurrence in HER2-positive, hormone-positive breast cancer, limited by severe diarrhoea.
OSE2101 is an experimental cancer vaccine from OSE Immunotherapeutics in phase 3 trials for non-small-cell lung cancer, aimed at HER2 and CEACAM5.
A second HER2 antibody that binds a different spot from trastuzumab, blocking HER2 from pairing with HER3; together they extended survival by 16 months in CLEOPATRA.
Poziotinib was a tablet designed to fit the awkward shape of HER2 and EGFR exon 20 mutations in lung cancer. It shrank tumours in some patients but caused severe rash and diarrhoea, and the FDA declined to approve it in 2022.
Pyrotinib is an irreversible pan-ErbB kinase inhibitor pill (EGFR, HER2, HER4) from Jiangsu Hengrui, approved in China since 2018 but not in the US or EU. It is the standard HER2 pill there, given with capecitabine after trastuzumab, and the comparator that new Chinese HER2 ADCs are beating; diarrhoea affects nearly every patient.
RO7771950 is an experimental small-molecule drug from Hoffmann-La Roche in phase 3 trials for HER2-positive breast cancer and HR-positive / HER2-negative breast cancer, aimed at HER2.
RPH-051 is an experimental monoclonal antibody from R-Pharm in phase 3 trials for HR-positive / HER2-negative breast cancer and HER2-positive breast cancer, aimed at HER2.
Sevabertinib is an oral HER2 inhibitor for lung cancers with HER2 mutations, approved in November 2025 as an alternative to Enhertu and zongertinib.
SSGJ-612 is an experimental monoclonal antibody from Shenyang Sunshine Pharmaceutical in phase 2 trials, aimed at HER2.
SSGJ-705 is an experimental monoclonal antibody from Shenyang Sunshine Pharmaceutical in phase 2 trials, aimed at PD-1 and HER2.
TQB2102 is an experimental antibody-drug conjugate from Chia Tai Tianqing Pharmaceutical Nanjing Shunxin Pharmaceutical in phase 3 trials for HR-positive / HER2-negative breast cancer, HER2-positive breast cancer and biliary tract cancer, aimed at HER2.
TQB2930 is an experimental bispecific antibody from Chia Tai Tianqing Pharmaceutical in phase 2 trials for HR-positive / HER2-negative breast cancer, aimed at HER2 and EGFR.
The first targeted antibody for a solid tumour (1998), which turned HER2-positive breast cancer from the worst subtype into one of the most treatable.
Near-identical copies of Herceptin, approved since 2017, that cut the price of HER2 treatment and widened access worldwide.
SystImmune's HER2 ADC, sharing its payload with iza-bren, now in a 1,450-patient trial to replace Kadcyla after surgery.
Trastuzumab deruxtecan (Enhertu) is the most successful ADC ever. It redefined HER2 by working in tumours with only tiny amounts of the protein, and in 2026 moved into early-stage breast cancer.
A HER2 ADC with a DNA-alkylating payload that beat chemotherapy in a phase 3 trial yet never reached the market, because eye and lung toxicity and a stronger rival arrived first.
Trastuzumab emtansine (Kadcyla, T-DM1) was the first ADC for a solid tumour (2013). It is still standard after surgery for HER2+ breast cancer patients whose tumour did not fully respond to pre-surgery treatment.
Trastuzumab pamirtecan is DualityBio and BioNTech's HER2 antibody-drug conjugate, in phase 3 trials in breast cancers with high and with modest HER2 expression and in HER2-expressing endometrial cancer.
Hengrui's HER2 ADC, approved in China for lung cancer and showing Enhertu-scale results in breast cancer, part of a wave of Chinese ADCs heading for global trials.
A HER2-selective pill that works in the brain, for HER2-positive breast cancer with brain metastases.
A pill that blocked the HER family of growth receptors, tested with capecitabine as second-line treatment for bile duct and gallbladder cancer. It did not beat capecitabine alone in the TreeTopp trial and development stopped.
Zanidatamab (Ziihera) is an antibody that grabs HER2 at two different spots, approved for HER2+ bile duct cancer.
Zanidatamab zovodotin joined the two-armed HER2 antibody zanidatamab to a cell-killing payload. It was tested in early trials in HER2-expressing cancers; the plain antibody went on to approval, the conjugate did not progress beyond phase 1.
Zenocutuzumab is the first drug for cancers driven by NRG1 gene fusions, working by blocking HER3 from receiving its growth signal.
Zongertinib was the first oral HER2 inhibitor for lung cancer with HER2 mutations, approved in 2025 and moved to first line in 2026.
The 48 most recent of 59 papers; see them all →
The IHC 3+ subgroup result is why the tumour-agnostic label is written at 3+ and not 2+, and why a gallbladder cancer with a strong HER2 stain now has two on-label choices (zanidatamab, trastuzumab deruxtecan) after chemotherapy. Lung toxicity again ran higher than in breast cancer.
Three-quarters of chemotherapy-naive TNBC would be low or ultralow by the DESTINY-Breast06 definitions, but ultralow is unlabelled in TNBC and carries no prognostic weight.
Targeted therapy prevalence estimates from one country may not hold in another, so a UK cohort, with its own ancestry mix, would need its own molecular survey before assuming HER2 or other rates from Asian or Latin American series.
A direct check of the HERIZON-BTC-01 testing algorithm in routine pathology: IHC 3+ can stand alone, 2+ needs ISH, and the low-level amplification in weakly stained tumours is the group where HER2 drugs are least likely to help.
For gallbladder cancer the points that matter are that HER2 can disappear under HER2-directed pressure, that SMAD4 co-mutation predicts a worse response, and that sequencing at progression, not just at diagnosis, may be needed to guide the next line.
Every KRAS wild-type pancreatic cancer should be tested for NRG1 fusions because a specific, approved antibody now exists; zenocutuzumab is the first targeted drug approved for a pancreatic cancer driver.
HER2 is as frequent in India as in the West, so HER2 testing pays off in the highest-incidence population, while tumour-agnostic immunotherapy markers will rarely apply. The paper also shows plasma testing is feasible where tissue is scarce.
Evidence that the immune environment of gallbladder cancer differs by population even when the mutations do not; a reason to report gallbladder cancer and its regions separately in immunotherapy trials rather than as one biliary subgroup.
Query for this target: (TITLE:"HER2" OR ABSTRACT:"HER2" OR TITLE:"ERBB2" OR ABSTRACT:"ERBB2") 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 HER2, not a curated reading list.
Shares Lemmon and Schlessinger 2010: cell signalling by receptor tyrosine kinases, Koichi Goto, Imagene AI, Amplification and the tags adc-target, driver.
Shares Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway, Imagene AI, Cogent Biosciences, Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer and the tag driver.
Shares Myricx Bio, Overexpression, Alpha radioligands after ADC failure, Deliver CAR-T cells straight into the fluid around the brain and the tag adc-target.
Shares Mayo Clinic Comprehensive Cancer Center in Florida, Re-map the tumour's surface proteins before choosing the next antibody drug, Mitosis & the spindle assembly checkpoint, Endometrial cancer and the tag adc-target.
Shares Overexpression, Mitosis & the spindle assembly checkpoint, Bispecific ADC, Bladder & urothelial cancer and the tag adc-target.
Shares Orum Therapeutics, Radio-antibody & radio-ADC, Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Dual-Target CAR-NK Cells for Advanced Breast Cancer HER2+ TNBC, Antibody-drug conjugate (ADC), Triple-negative breast cancer (TNBC) and the tag adc-target.
Shares Dual-Target CAR-NK Cells Directed Against MSLN, EGFR, or HER2 in Advanced NSCLC, Dual-Target CAR-NK Cells Targeting MSLN, EGFR, or HER2 in Advanced NSCLC, Varlitinib, A Phase 1/2, Open-label, Multicenter, FIH Study to Evaluate Safety, Tolerability, PK and Anti-tumor Activity of YH42946 and the tag driver.