# HER2

Source: https://onco.cc/targets/her2/  
OnCo record `her2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Tags: adc-target; driver
- Symbol: ERBB2
- Class: surface-antigen
- Biology: 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.
- Where found: HER2+ breast cancer (~15-20%); HER2-low breast cancer (~50%); Gastric/GEJ (~15-20%); HER2-mutant NSCLC (~2-3%); Colorectal (~3-5%); Biliary tract; Triple-negative breast cancer: her2-low (ihc 1+ or 2+/ish-negative) 24-37%; Triple-negative breast cancer: her2-ultralow (ihc 0 with faint membrane staining in 10% or fewer cells) about 38%; Pancreatic ductal adenocarcinoma: amplification (mutation in a further 1%) 1-5%; Colorectal cancer: high-level amplification 2-3%; Colorectal cancer: activating mutation (not amplification) 4-6%; Gallbladder cancer: amplification 8-10%; Gallbladder cancer: activating mutation (s310f/y hotspot) 4-8%; Gallbladder cancer: protein overexpression (ihc) 9-31%; Non-small-cell lung cancer: exon 20 insertion and kinase-domain missense 2-4%; Non-small-cell lung cancer: high-level amplification 1-3%

## Notes

- Triple-negative breast cancer, HER2-low and ultralow: HER2-low (IHC 1+ or 2+/ISH-negative) in 36.6% of TNBC among 3,689 HER2-negative patients (Schettini 2021) and 34.0% of 1,162 hormone receptor-negative trial patients (Denkert 2021); HER2-null 38.4%, ultralow 37.6% and low 24.0% of 367 untreated TNBCs (Boissiere-Michot 2026). DESTINY-Breast04 enrolled 63 hormone receptor-negative patients (Modi 2022) and the HER2-low label covers them; DESTINY-Breast06 and the ultralow label are hormone receptor-positive only. In TNBC no gene separates HER2-low from HER2-0 and pathologist agreement is poor (Schettini 2021).
- Pancreatic ductal adenocarcinoma: ERBB2 amplification in 1 to 5% by platform and mutation in under 1% (cBioPortal); amplification in 2.2% of KRAS wild-type tumours (Philip 2022). It was among the druggable focal amplifications found at low individual prevalence in 100 whole genomes (Waddell 2015); zenocutuzumab reaches HER2 as the docking arm of its NRG1-blocking mechanism rather than as an amplified driver.
- Colorectal cancer: ERBB2 amplification in 2 to 3% of all tumours but 5.3% of RAS and BRAF wild-type ones, which is the population that matters because it overlaps exactly with the patients an EGFR antibody would otherwise be given to (cBioPortal; Richman 2016; 48 of 914 screened for HERACLES). The threshold is the HERACLES criterion, intense membranous staining in more than 50% of cells corresponding to homogeneous amplification, not the 10% used in gastric cancer (Valtorta 2015). HER2 amplification was first proposed as a cause of cetuximab resistance in patient-derived xenografts (Bertotti 2011), and the regimens that followed are trastuzumab plus lapatinib (HERACLES, 30% response), tucatinib plus trastuzumab (MOUNTAINEER) and trastuzumab deruxtecan (DESTINY-CRC02). Plasma HER2 copy number selects patients as well as tissue does (Nakamura 2021). ERBB2 point mutations, 4 to 6%, are mostly passengers in hypermutated tumours and do not qualify.
- Gallbladder cancer, amplification versus mutation: ERBB2 alterations were present in 14% of 260 patients, as 8% amplification alone, 4% mutation alone, 1.5% both and 0.4% fusion (Mondaca 2024, MSK-IMPACT), and in 15% of 376 Indian patients with about 8% amplification and an S310F/Y hotspot (Suryavanshi 2025). Only the amplified tumours are seen by IHC and ISH, which is what the zanidatamab label tests for (IHC 3+); the extracellular S310 and kinase-domain mutations need sequencing and are not covered by that label. Protein positivity depends on the scoring rule: 31.3% of 80 resected Japanese gallbladder carcinomas by the gastric guideline (Hiraoka 2020), 12.8% of 187 Chilean cases by breast criteria (Roa 2014), 9.4% of 53 by HERIZON-BTC-01 criteria (Angerilli 2026). ERBB2-driven biliary tumours can lose ERBB2 at progression (Cowzer 2026).
- Lung cancer: a mutation target rather than an amplification target, the opposite of breast and stomach cancer. Exon 20 insertions are 1.9 to 2.2% of adenocarcinomas and 3.4% of never-smoker cases, with Y772_A775dup the dominant allele; any ERBB2 mutation reaches about 4%, and amplification, 1 to 3%, is a separate event that the licensed oral inhibitors do not select on (cBioPortal; Kris 2014). Amplification also appears as acquired resistance to EGFR blockade, in 3 of 24 rebiopsied patients (Yu 2013). Immunohistochemistry has no selective role here.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/HER2/neu
- Wikipedia: https://en.wikipedia.org/wiki/HER2/neu

## Connected records

- biomarkers: [HER2 (ERBB2) activating mutation](https://onco.cc/biomarkers/her2-mutation/), [HER2 IHC 0 (HER2-negative, including ultralow)](https://onco.cc/biomarkers/her2-ihc-0/), [HER2 IHC 1+](https://onco.cc/biomarkers/her2-ihc-1-plus/), [HER2 IHC 2+ (equivocal, reflex to ISH)](https://onco.cc/biomarkers/her2-ihc-2-plus/), [HER2 IHC 3+ (HER2-positive by immunohistochemistry)](https://onco.cc/biomarkers/her2-ihc-3-plus/), [HER2 ISH amplified (ERBB2 gene amplification)](https://onco.cc/biomarkers/her2-ish-amplified/), [HER2-low (IHC 1+ or IHC 2+/ISH-negative)](https://onco.cc/biomarkers/her2-low-ihc/), [HER2-ultralow (IHC 0 with membrane staining)](https://onco.cc/biomarkers/her2-ultralow/), [NRG1 gene fusion](https://onco.cc/biomarkers/nrg1-fusion/)
- cancers: [Advanced and metastatic small bowel adenocarcinoma](https://onco.cc/cancers/advanced-small-bowel-adenocarcinoma/), [Ampullary cancer (ampulla of Vater)](https://onco.cc/cancers/ampullary/), [Apocrine carcinoma of the breast](https://onco.cc/cancers/apocrine-carcinoma-breast/), [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Cancer of unknown primary (CUP)](https://onco.cc/cancers/cancer-of-unknown-primary/), [Cancer of unknown primary, unfavourable (adenocarcinoma and poorly differentiated carcinoma)](https://onco.cc/cancers/cup-unfavourable/), [Cervical cancer](https://onco.cc/cancers/cervical/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Ductal carcinoma in situ (DCIS)](https://onco.cc/cancers/ductal-carcinoma-in-situ/), [Early-onset colorectal cancer (under 50)](https://onco.cc/cancers/early-onset-colorectal/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Extrahepatic cholangiocarcinoma (perihilar and distal)](https://onco.cc/cancers/extrahepatic-cholangiocarcinoma/), [Gallbladder adenocarcinoma](https://onco.cc/cancers/gallbladder-adenocarcinoma/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [HER2-amplified colorectal cancer](https://onco.cc/cancers/her2-amplified-colorectal/), [HER2-mutant non-small-cell lung cancer](https://onco.cc/cancers/her2-mutant-nsclc/), [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [HER2-positive gastric cancer](https://onco.cc/cancers/gastric-her2-positive/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Localised small bowel adenocarcinoma (stage I to III, resected)](https://onco.cc/cancers/localised-small-bowel-adenocarcinoma/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Male breast cancer](https://onco.cc/cancers/male-breast-cancer/), [Mucinous ovarian cancer](https://onco.cc/cancers/mucinous-ovarian-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Oesophageal and junctional adenocarcinoma](https://onco.cc/cancers/oesophageal-adenocarcinoma/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Osteosarcoma](https://onco.cc/cancers/osteosarcoma/), [p53-abnormal endometrial cancer, including uterine serous carcinoma](https://onco.cc/cancers/endometrial-p53-abnormal/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Recurrent or metastatic cervical cancer](https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/), [Salivary duct carcinoma](https://onco.cc/cancers/salivary-duct-carcinoma/), [Salivary gland cancers](https://onco.cc/cancers/salivary-gland/), [Small intestine cancer (small bowel adenocarcinoma)](https://onco.cc/cancers/small-bowel/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/), [Uterine carcinosarcoma](https://onco.cc/cancers/uterine-carcinosarcoma/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Bispecific ADC](https://onco.cc/technologies/bispecific-adc/), [HER2 PET](https://onco.cc/technologies/her2-pet/), [HER2 tyrosine kinase inhibitors](https://onco.cc/technologies/her2-tyrosine-kinase-inhibitors/), [Immuno-PET](https://onco.cc/technologies/immuno-pet/), [Parsortix label-free circulating tumour cell harvest](https://onco.cc/technologies/parsortix-ctc-harvest/), [Radio-antibody & radio-ADC](https://onco.cc/technologies/radioimmunotherapy/)
- drugs: [A166](https://onco.cc/drugs/a166/), [ABSK061](https://onco.cc/drugs/absk061/), [Afatinib](https://onco.cc/drugs/afatinib/), [ARX788](https://onco.cc/drugs/arx788/), [AVZO-021](https://onco.cc/drugs/avzo-021/), [Cinrebafusp alfa](https://onco.cc/drugs/cinrebafusp-alfa/), [Disitamab vedotin](https://onco.cc/drugs/disitamab-vedotin/), [GLSI-100](https://onco.cc/drugs/glsi-100/), [GQ1005](https://onco.cc/drugs/gq1005/), [HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)](https://onco.cc/drugs/her2-testing-assays/), [HLX11](https://onco.cc/drugs/hlx11/), [HLX22](https://onco.cc/drugs/hlx22/), [IAH0968](https://onco.cc/drugs/iah0968/), [IBI354](https://onco.cc/drugs/ibi354/), [Inetetamab](https://onco.cc/drugs/inetetamab/), [KN026](https://onco.cc/drugs/kn026/), [Lapatinib](https://onco.cc/drugs/lapatinib/), [Margetuximab](https://onco.cc/drugs/margetuximab/), [Neratinib](https://onco.cc/drugs/neratinib/), [OSE2101](https://onco.cc/drugs/ose2101/), [Pertuzumab](https://onco.cc/drugs/pertuzumab/), [Poziotinib](https://onco.cc/drugs/poziotinib/), [Pyrotinib](https://onco.cc/drugs/pyrotinib/), [RO7771950](https://onco.cc/drugs/ro7771950/), [RPH-051](https://onco.cc/drugs/rph-051/), [Sevabertinib](https://onco.cc/drugs/sevabertinib/), [SSGJ-612](https://onco.cc/drugs/ssgj-612/), [SSGJ-705](https://onco.cc/drugs/ssgj-705/), [TQB2102](https://onco.cc/drugs/tqb2102/), [TQB2930](https://onco.cc/drugs/tqb2930/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab biosimilars](https://onco.cc/drugs/trastuzumab-biosimilars/), [Trastuzumab brengitecan](https://onco.cc/drugs/trastuzumab-brengitecan/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [Trastuzumab duocarmazine](https://onco.cc/drugs/trastuzumab-duocarmazine/), [Trastuzumab emtansine](https://onco.cc/drugs/trastuzumab-emtansine/), [Trastuzumab pamirtecan](https://onco.cc/drugs/trastuzumab-pamirtecan/), [Trastuzumab rezetecan](https://onco.cc/drugs/trastuzumab-rezetecan/), [Tucatinib](https://onco.cc/drugs/tucatinib/), [Varlitinib](https://onco.cc/drugs/varlitinib/), [Zanidatamab](https://onco.cc/drugs/zanidatamab/), [Zanidatamab zovodotin](https://onco.cc/drugs/zanidatamab-zovodotin/), [Zenocutuzumab](https://onco.cc/drugs/zenocutuzumab/), [Zongertinib](https://onco.cc/drugs/zongertinib/)
- companies: [Alphamab Oncology](https://onco.cc/companies/alphamab/), [Ambrx](https://onco.cc/companies/ambrx/), [Amunix Pharmaceuticals](https://onco.cc/companies/amunix-pharmaceuticals/), [Biocon Biologics](https://onco.cc/companies/biocon-biologics/), [Callio Therapeutics](https://onco.cc/companies/callio-therapeutics/), [Cogent Biosciences](https://onco.cc/companies/cogent-biosciences/), [Dantari](https://onco.cc/companies/dantari/), [Duality Biotherapeutics](https://onco.cc/companies/dualitybio/), [Enliven Therapeutics](https://onco.cc/companies/enliven-therapeutics/), [Galena Biopharma](https://onco.cc/companies/galena-biopharma/), [Glenmark Pharmaceuticals (Ichnos Glenmark Innovation)](https://onco.cc/companies/glenmark/), [Iambic Therapeutics](https://onco.cc/companies/iambic-therapeutics/), [Ibex Medical Analytics](https://onco.cc/companies/ibex-medical-analytics/), [Iksuda Therapeutics](https://onco.cc/companies/iksuda-therapeutics/), [Imagene AI](https://onco.cc/companies/imagene-ai/), [Myricx Bio](https://onco.cc/companies/myricx-bio/), [Orum Therapeutics](https://onco.cc/companies/orum-therapeutics/), [Precirix](https://onco.cc/companies/precirix/)
- pathways: [Bladder cancer (KEGG map)](https://onco.cc/pathways/bladder-cancer-signalling/), [Breast cancer (KEGG map)](https://onco.cc/pathways/breast-cancer-signalling/), [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [DNA replication & origin licensing](https://onco.cc/pathways/dna-replication-licensing/), [Drivers, passengers & the two-hit model](https://onco.cc/pathways/oncogene-activation-two-hit/), [Drug efflux pumps (ABC transporters)](https://onco.cc/pathways/drug-efflux-pumps/), [Endometrial cancer (KEGG map)](https://onco.cc/pathways/endometrial-cancer-signalling/), [Gastric cancer (KEGG map)](https://onco.cc/pathways/gastric-cancer-signalling/), [Mitosis & the spindle assembly checkpoint](https://onco.cc/pathways/mitotic-spindle-checkpoint/), [NK-cell recognition: missing self & stress ligands](https://onco.cc/pathways/nk-cell-recognition/), [Organ tropism: seed and soil](https://onco.cc/pathways/organ-tropism-seed-soil/), [Pancreatic cancer (KEGG map)](https://onco.cc/pathways/pancreatic-cancer-signalling/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/), [The blood-brain barrier & brain metastasis](https://onco.cc/pathways/blood-brain-barrier-metastasis/)
- terms: [Amplification](https://onco.cc/terms/amplification/), [Antigen](https://onco.cc/terms/antigen/), [Co-amplification and the 17q12 HER2 amplicon](https://onco.cc/terms/co-amplification/), [Dual HER2 blockade](https://onco.cc/terms/dual-her2-blockade/), [Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)](https://onco.cc/terms/endometrial-molecular-classes/), [Epitope](https://onco.cc/terms/epitope/), [Gene amplification and copy-number change](https://onco.cc/terms/gene-amplification/), [Hallmark: sustaining proliferative signalling](https://onco.cc/terms/sustaining-proliferative-signaling/), [HER2 and genomic testing for biliary cancer on the NHS](https://onco.cc/terms/genomic-testing-biliary-uk/), [HER2 testing in biliary tract cancer (IHC, ISH and NGS)](https://onco.cc/terms/her2-testing-in-biliary-cancer/), [HER2-low and HER2-ultralow](https://onco.cc/terms/her2-low/), [HER2-low eligibility for trastuzumab deruxtecan, and TROP2 ADCs without a test (triple-negative disease)](https://onco.cc/terms/her2-low-and-trop2-adc-eligibility-tnbc/), [HER2-positive (IHC 3+ or ISH-amplified)](https://onco.cc/terms/her2-positive/), [HERACLES criteria (HER2 in bowel cancer)](https://onco.cc/terms/heracles-criteria/), [HGNC gene symbol](https://onco.cc/terms/hgnc-symbol/), [Intrahepatic, perihilar, distal and gallbladder cancer](https://onco.cc/terms/biliary-anatomy-subtypes/), [Oncogene](https://onco.cc/terms/oncogene/), [Overexpression](https://onco.cc/terms/overexpression/), [Receptor](https://onco.cc/terms/receptor/), [Somatic mutation theory of cancer](https://onco.cc/terms/somatic-mutation-theory/)
- trials: [A Phase 1/2, Open-label, Multicenter, FIH Study to Evaluate Safety, Tolerability, PK and Anti-tumor Activity of YH42946](https://onco.cc/trials/nct06616766/), [A Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of YL202 in Patients With BC](https://onco.cc/trials/nct06439771/), [Beamion LUNG-1](https://onco.cc/trials/beamion-lung-1/), [CLEOPATRA](https://onco.cc/trials/cleopatra/), [Clinical Trial of YH32367 in Patients With HER2 Positive Locally Advanced or Metastatic Solid Tumor](https://onco.cc/trials/nct05523947/), [DESTINY-CRC01](https://onco.cc/trials/destiny-crc01/), [DESTINY-CRC02](https://onco.cc/trials/destiny-crc02/), [DESTINY-Gastric04](https://onco.cc/trials/destiny-gastric04/), [DESTINY-Lung02](https://onco.cc/trials/destiny-lung02/), [DESTINY-PanTumor02](https://onco.cc/trials/destiny-pantumor02/), [DETERMINE arm 04: trastuzumab with pertuzumab in HER2-amplified or mutated rare cancers](https://onco.cc/trials/determine-arm04/), [Dual-Target CAR-NK Cells Directed Against MSLN, EGFR, or HER2 in Advanced NSCLC](https://onco.cc/trials/nct07467863/), [Dual-Target CAR-NK Cells for Advanced Breast Cancer HER2+ TNBC](https://onco.cc/trials/nct07510802/), [Dual-Target CAR-NK Cells for Biomarker-Selected Advanced Colorectal Cancer](https://onco.cc/trials/nct07462650/), [Dual-Target CAR-NK Cells Targeting MSLN, EGFR, or HER2 in Advanced NSCLC](https://onco.cc/trials/nct07641023/), [Dual-Targeting CAR-NK Cells in Biomarker-Selected Advanced Colorectal Cancer](https://onco.cc/trials/nct07589517/), [First-In-Human Study of STX-721/PFL-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR or HER2 Exon 20 Insertion Mutations](https://onco.cc/trials/nct06043817/), [Gene Therapy for HER-Positive Cancer (SENTRY-HER2)](https://onco.cc/trials/nct07192432/), [HER2 Targeted Molecular Imaging in mBC and Other Metastatic Solid Carcinomas Using 68Ga-ABS011](https://onco.cc/trials/nct06369831/), [HER2CLIMB](https://onco.cc/trials/her2climb/), [HERA, NSABP B-31 & NCCTG N9831 (adjuvant trastuzumab)](https://onco.cc/trials/hera-b31-n9831/), [HERIZON-BTC-01](https://onco.cc/trials/herizon-btc-01/), [HERIZON-BTC-302](https://onco.cc/trials/herizon-btc-302/), [HERIZON-GEA-01](https://onco.cc/trials/herizon-gea-01/), [KRISTINE](https://onco.cc/trials/kristine/), [MOUNTAINEER](https://onco.cc/trials/mountaineer/), [MOUNTAINEER-03](https://onco.cc/trials/mountaineer-03/), [Phase 1b/2 Study to Evaluate ABT-101 in Solid Tumor and NSCLC Patients](https://onco.cc/trials/nct05532696/), [SAFIR-ABC10](https://onco.cc/trials/safir-abc10/), [SOHO-01](https://onco.cc/trials/soho-01/), [Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Gastric Cancer](https://onco.cc/trials/nct05771584/), [ToGA](https://onco.cc/trials/toga/), [TRAIN-2](https://onco.cc/trials/train-2/), [TRAP-BTC](https://onco.cc/trials/trap-btc/), [TreeTopp](https://onco.cc/trials/treetopp/), [TRIUMPH](https://onco.cc/trials/triumph/)
- key papers: [A molecularly annotated platform of patient-derived xenografts identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer](https://onco.cc/key-papers/paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011/), [Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers](https://onco.cc/key-papers/paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013/), [Assessment of a HER2 scoring system for colorectal cancer: results from a validation study](https://onco.cc/key-papers/paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015/), [Biliary cancer: utility of next-generation sequencing for clinical management](https://onco.cc/key-papers/paper-javle-biliary-ngs-cancer-2016/), [CD74-NRG1 fusions in lung adenocarcinoma](https://onco.cc/key-papers/paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014/), [Circulating tumor DNA profiling of advanced biliary tract cancers](https://onco.cc/key-papers/paper-mody-biliary-ctdna-profiling-jco-po-2019/), [Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial (TRIUMPH)](https://onco.cc/key-papers/paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021/), [Clinical and genomic characterization of ERBB2-altered gallbladder cancer: exploring differences between an American and a Chilean cohort](https://onco.cc/key-papers/paper-mondaca-erbb2-gallbladder-us-chile-jco-go-2024/), [Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials](https://onco.cc/key-papers/paper-denkert-her2-low-pooled-neoadjuvant-lancet-oncol-2021/), [Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer](https://onco.cc/key-papers/paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019/), [Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer](https://onco.cc/key-papers/paper-schettini-her2-low-features-npj-breast-cancer-2021/), [Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention](https://onco.cc/key-papers/paper-giraldo-gallbladder-msk-impact-ccr-2022/), [Comprehensive molecular characterization of human colon and rectal cancer](https://onco.cc/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/), [Comprehensive molecular profiling of lung adenocarcinoma](https://onco.cc/key-papers/paper-tcga-lung-adenocarcinoma-nature-2014/), [DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer](https://onco.cc/key-papers/paper-destiny-breast03-nejm-2022/), [DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group](https://onco.cc/key-papers/paper-destiny-breast04-nejm-2022/), [DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer](https://onco.cc/key-papers/paper-destiny-breast06-nejm-2024/), [Details of human epidermal growth factor receptor 2 status in 454 cases of biliary tract cancer](https://onco.cc/key-papers/paper-hiraoka-her2-status-biliary-hum-pathol-2020/), [Detection of NRG1 gene fusions in solid tumors](https://onco.cc/key-papers/paper-jonna-nrg1-fusions-solid-tumours-ccr-2019/), [Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features](https://onco.cc/key-papers/paper-missiaglia-distal-proximal-colon-cancers-ann-oncol-2014/), [Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES)](https://onco.cc/key-papers/paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016/), [Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing biliary tract or pancreatic tumors: a subgroup analysis of DESTINY-PanTumor02](https://onco.cc/key-papers/paper-oh-destiny-pantumor02-biliary-pancreatic-esmo-open-2026/), [eNRGy: efficacy of zenocutuzumab in NRG1 fusion-positive cancer](https://onco.cc/key-papers/paper-enrgy-zenocutuzumab-nrg1-fusion-positive-cancer-nejm-2025/), [Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status](https://onco.cc/key-papers/paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026/), [Genomic and evolutionary classification of lung cancer in never smokers](https://onco.cc/key-papers/paper-zhang-lung-cancer-never-smokers-nat-genet-2021/), [Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies](https://onco.cc/key-papers/paper-jiang-fuscc-tnbc-landscape-cancer-cell-2019/), [Genomic landscape of lung adenocarcinoma in East Asians](https://onco.cc/key-papers/paper-chen-east-asian-lung-adenocarcinoma-nat-genet-2020/), [Genomic profiling of Indian gallbladder carcinoma: mutational insights in a high-incidence population](https://onco.cc/key-papers/paper-suryavanshi-indian-gallbladder-genomics-jco-go-2025/), [Genomic spectra of biliary tract cancer](https://onco.cc/key-papers/paper-nakamura-biliary-genomic-spectra-nat-genet-2015/), [Geographic and genetic diversity in gallbladder cancer mutation profiles: insights from a worldwide exome analysis](https://onco.cc/key-papers/paper-garate-calderon-gallbladder-cancer-worldwide-exome-ebiomedicine-2026/), [HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials](https://onco.cc/key-papers/paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016/), [HER2 status in extrahepatic cholangiocarcinoma and gallbladder carcinoma: concordance between immunohistochemistry and chromogenic in situ hybridization in 140 cases](https://onco.cc/key-papers/paper-angerilli-her2-ihc-cish-biliary-hum-pathol-2026/), [HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?](https://onco.cc/key-papers/paper-galdy-her2-biliary-tract-meta-analysis-cancer-metastasis-rev-2017/), [KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment](https://onco.cc/key-papers/paper-katherine-nejm-2019/), [Lemmon and Schlessinger 2010: cell signalling by receptor tyrosine kinases](https://onco.cc/key-papers/paper-lemmon-schlessinger-rtk-signalling-cell-2010/), [Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer](https://onco.cc/key-papers/paper-cowzer-biliary-targeted-therapy-determinants-ccr-2026/), [Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/), [Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets](https://onco.cc/key-papers/paper-weinberg-biliary-profiling-jgo-2019/), [NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer](https://onco.cc/key-papers/paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019/), [Overexpression of the HER2/neu gene: a new therapeutic possibility for patients with advanced gallbladder cancer](https://onco.cc/key-papers/paper-roa-her2-overexpression-gallbladder-gcr-2014/), [Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study](https://onco.cc/key-papers/paper-javle-mypathway-her2-biliary-lancet-oncol-2021/), [Population-Specific Immunogenomic Alterations in Gallbladder Cancer and Prognostic Significance](https://onco.cc/key-papers/paper-zhu-population-specific-immunogenomics-gallbladder-cancer-mod-pathol-2025/), [Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies](https://onco.cc/key-papers/paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017/), [Recurrent R-spondin fusions in colon cancer](https://onco.cc/key-papers/paper-seshagiri-rspo-fusions-colon-nature-2012/), [Slamon 1987: HER2 gene amplification marks an aggressive form of breast cancer](https://onco.cc/key-papers/paper-slamon-her2-amplification-science-1987/), [Slamon 1989: HER2/neu in human breast and ovarian cancer](https://onco.cc/key-papers/paper-slamon-her2-breast-ovarian-science-1989/), [Slamon 2001: adding trastuzumab to chemotherapy for HER2-positive metastatic breast cancer](https://onco.cc/key-papers/paper-slamon-trastuzumab-nejm-2001/), [The mutational landscape and actionable targets of gallbladder cancer: an ancestry-informed and comparative analysis of a Chilean population](https://onco.cc/key-papers/paper-erices-chilean-gallbladder-landscape-front-oncol-2025/), [ToGA (Bang 2010): trastuzumab with chemotherapy for HER2-positive advanced gastric cancer](https://onco.cc/key-papers/paper-toga-trastuzumab-gastric-lancet-2010/), [Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01)](https://onco.cc/key-papers/paper-siena-destiny-crc01-trastuzumab-deruxtecan-lancet-oncol-2021/), [Trastuzumab deruxtecan in human epidermal growth factor receptor 2-expressing biliary tract cancer (HERB; NCCH1805): a multicenter, single-arm, phase II trial](https://onco.cc/key-papers/paper-ohba-herb-trastuzumab-deruxtecan-biliary-jco-2024/), [Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial](https://onco.cc/key-papers/paper-destiny-crc02-lancet-oncol-2024/), [Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER)](https://onco.cc/key-papers/paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023/), [Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors](https://onco.cc/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/), [Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs](https://onco.cc/key-papers/paper-kris-lung-cancer-mutation-consortium-jama-2014/), [Whole genomes redefine the mutational landscape of pancreatic cancer](https://onco.cc/key-papers/paper-waddell-whole-genomes-pancreatic-nature-2015/), [Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway](https://onco.cc/key-papers/paper-li-gallbladder-exome-erbb-nat-genet-2014/), [Yarden and Sliwkowski 2001: untangling the ErbB signalling network](https://onco.cc/key-papers/paper-yarden-sliwkowski-erbb-network-nrmcb-2001/), [Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study](https://onco.cc/key-papers/paper-harding-lancet-oncol/)
- pairings: [HER2 sequence in gastric cancer: zanidatamab/trastuzumab + chemo ± PD-1 → T-DXd](https://onco.cc/pairings/her2-gastric-sequence/)
- ideas: [A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer](https://onco.cc/ideas/idea-tnbc-adc-sequencing-trial/), [Alpha radioligands after ADC failure](https://onco.cc/ideas/idea-alpha-after-adc/), [An abbreviated approval path for follow-on antibodies within a validated class](https://onco.cc/ideas/idea-fund-abbreviated-pathway-me-too-biologics/), [Biomarker-directed first-line quadruplets in gastric cancer](https://onco.cc/ideas/idea-biomarker-quadruplet-gastric/), [Bispecific antibodies that engage macrophages instead of T cells](https://onco.cc/ideas/idea-bio2-myeloid-engager-bispecific/), [Deliver CAR-T cells straight into the fluid around the brain](https://onco.cc/ideas/idea-bio2-intraventricular-car-t/), [Dual-payload ADCs in first line to prevent resistance](https://onco.cc/ideas/idea-dual-payload-first/), [HER2 ADCs as standard for HER2-positive serous endometrial cancer](https://onco.cc/ideas/idea-her2-adc-serous-endometrial/), [Re-map the tumour's surface proteins before choosing the next antibody drug](https://onco.cc/ideas/idea-bio1-antigen-mapping-at-progression/), [Reflex HER2 testing of every advanced gallbladder and extrahepatic biliary cancer](https://onco.cc/ideas/idea-gbc-reflex-her2-testing-advanced-biliary/), [Reflex re-scoring of HER2 0 versus 1+ with digital assistance so every eligible triple-negative patient reaches trastuzumab deruxtecan](https://onco.cc/ideas/idea-tnbc-her2-ultralow-testing-uptake/), [Use the brain's own transport door to carry antibody drugs across](https://onco.cc/ideas/idea-bio2-transferrin-shuttle-adc/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/), [Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials](https://onco.cc/roadmaps/gallbladder-cancer-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- targets: [CD137 (4-1BB, TNFRSF9)](https://onco.cc/targets/cd137/), [GRB7](https://onco.cc/targets/grb7/), [MIEN1](https://onco.cc/targets/mien1/), [PGAP3](https://onco.cc/targets/pgap3/), [PNMT](https://onco.cc/targets/pnmt/), [PTK6 (BRK)](https://onco.cc/targets/ptk6/), [STARD3](https://onco.cc/targets/stard3/)
- institutions: [Georgetown Lombardi Comprehensive Cancer Center](https://onco.cc/institutions/georgetown-lombardi/), [Hospital del Mar / Hospital del Mar Research Institute](https://onco.cc/institutions/hospital-del-mar/), [Instituto Alexander Fleming](https://onco.cc/institutions/instituto-alexander-fleming/), [IRCCS Ospedale San Raffaele](https://onco.cc/institutions/san-raffaele/), [Istituto di Candiolo IRCCS (FPO)](https://onco.cc/institutions/candiolo/), [Mayo Clinic Comprehensive Cancer Center in Florida](https://onco.cc/institutions/mayo-clinic-florida/), [National Cancer Center Hospital East](https://onco.cc/institutions/ncc-hospital-east/), [Peking University Cancer Hospital](https://onco.cc/institutions/pku-cancer-hospital/), [Rosalind and Morris Goodman Cancer Institute, McGill University](https://onco.cc/institutions/mcgill-goodman/), [UCLA Jonsson Comprehensive Cancer Center](https://onco.cc/institutions/ucla-jonsson/), [Weizmann Institute of Science](https://onco.cc/institutions/weizmann/)
- people: [Barbara Bradfield](https://onco.cc/people/barbara-bradfield/), [Binghe Xu](https://onco.cc/people/xu-binghe/), [Bob T. Li](https://onco.cc/people/bob-li/), [Charles E. Geyer Jr.](https://onco.cc/people/charles-geyer/), [Cristina Saura](https://onco.cc/people/cristina-saura/), [Dennis J. Slamon](https://onco.cc/people/dennis-slamon/), [Fei Ma](https://onco.cc/people/ma-fei/), [Funda Meric-Bernstam](https://onco.cc/people/funda-meric-bernstam/), [Giuseppe Curigliano](https://onco.cc/people/giuseppe-curigliano/), [Helena Earl](https://onco.cc/people/helena-earl/), [Ian E. Krop](https://onco.cc/people/ian-krop/), [Jason S. Lewis](https://onco.cc/people/jason-lewis/), [Javier Cortés](https://onco.cc/people/javier-cortes/), [Jeeyun Lee](https://onco.cc/people/lee-jeeyun/), [Joaquín Arribas](https://onco.cc/people/joaquin-arribas/), [Joohyuk Sohn](https://onco.cc/people/sohn-joohyuk/), [Kohei Shitara](https://onco.cc/people/shitara-kohei/), [Koichi Goto](https://onco.cc/people/goto-koichi/), [Nancy U. Lin](https://onco.cc/people/nancy-lin/), [Sandra M. Swain](https://onco.cc/people/sandra-swain/), [Sara A. Hurvitz](https://onco.cc/people/sara-hurvitz/), [Sara M. Tolaney](https://onco.cc/people/sara-tolaney/), [Shanu Modi](https://onco.cc/people/shanu-modi/), [Sung-Bae Kim](https://onco.cc/people/kim-sung-bae/), [Tanios Bekaii-Saab](https://onco.cc/people/tanios-bekaii-saab/), [Yelena Y. Janjigian](https://onco.cc/people/yelena-janjigian/), [Yeon Hee Park](https://onco.cc/people/park-yeon-hee/), [Yosef Yarden](https://onco.cc/people/yosef-yarden/), [Yung-Jue Bang](https://onco.cc/people/bang-yung-jue/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Incentives reward me-too drugs and marginal gains](https://onco.cc/bottlenecks/b-incentive-misalignment/), [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/)

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JSON: https://onco.cc/api/v1/entities/her2.json