HER2
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
20 products aim at HER2: antibodies, antibody-drug conjugates, bispecific antibodies and small molecules. 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.
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.
- HER2+ breast cancer (~15-20%)
- HER2-low breast cancer (~50%)
- Gastric/GEJ (~15-20%)
- HER2-mutant NSCLC (~2-3%)
- Colorectal (~3-5%)
- Biliary tract
How common it is, by cancer
| 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 | 30-40% | HER2-low (IHC 1+ or 2+/ISH-) | Nature | |
| 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 |
| Colorectal cancer | 3-5% | Amplification/IHC 3+ | RAS wild-type enriched | Wikipedia |
| Non-small-cell lung cancer | 2-3% | ERBB2 exon 20 mutation | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Afatinib (Gilotrif) is an irreversible EGFR pill for lung cancer, notable for activity against uncommon EGFR mutations (G719X, L861Q, S768I).
ARX788 is a HER2 ADC with a precisely placed, non-cleavable payload that beat lapatinib-capecitabine in China and showed activity in brain metastases.
Disitamab vedotin is a Chinese HER2 ADC approved for gastric and bladder cancer, now in global trials with Pfizer.
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.
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.
Pyrotinib is China's HER2 pill, widely used there with capecitabine and as a comparator for the new Chinese HER2 ADCs.
Sevabertinib is an oral HER2 inhibitor for lung cancers with HER2 mutations, approved in November 2025 as an alternative to Enhertu and zongertinib.
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.
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.
Zanidatamab (Ziihera) is an antibody that grabs HER2 at two different spots, approved for HER2+ bile duct cancer.
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.
Patients with hormone-receptor-positive metastatic breast cancer that has stopped responding to endocrine therapy can be offered trastuzumab deruxtecan as their first chemotherapy-type treatment if the tumour shows any HER2 staining, rather than waiting until after conventional chemotherapy. Whether to use it before or after chemotherapy is now a choice, since overall survival was not shown to differ and the drug carries a risk of lung inflammation.
For HER2-positive metastatic breast cancer that has progressed after trastuzumab and a taxane, trastuzumab deruxtecan is now the standard second-line treatment and T-DM1 has moved later in the sequence. The benefit is large enough that ADC design, not just the target, is understood to be what matters. Patients need lung monitoring because of the risk of pneumonitis.
Patients whose breast cancer was previously called HER2-negative may now be eligible for an effective HER2-directed drug if their tumour has even low-level HER2 staining, so pathology reports must now distinguish HER2-low (1+ or 2+/ISH-negative) from HER2-zero. This applies to metastatic disease after at least one line of chemotherapy; it does not mean these patients benefit from trastuzumab or other older HER2 drugs.
HER2-positive breast cancer is now routinely treated before surgery so that the pathology result can guide what comes after: patients with no residual cancer continue trastuzumab (with or without pertuzumab), while those with residual disease switch to T-DM1. This model of using the tumour's response as a test has since been copied in triple-negative and other cancers.
Latest papers
topQuery 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.
Pages like this
not linked directly; found by shared links- TargetMET
Shares Amplification, Koichi Goto, Istituto di Candiolo IRCCS – FPO, Bispecific ADC and the tags adc-target, driver.
- TargetB7-H3
Shares Duality Biotherapeutics, Overexpression, Alpha radioligands after ADC failure, Deliver CAR-T cells straight into the fluid around the brain and the tag adc-target.
- TargetKRAS
Shares Tanios Bekaii-Saab, Oncogene, Istituto di Candiolo IRCCS – FPO, Hallmark: sustaining proliferative signalling and the tag driver.
- TargetTROP2
Shares Overexpression, Alpha radioligands after ADC failure, Bispecific antibodies that engage macrophages instead of T cells, Dual-payload ADCs in first line to prevent resistance and the tag adc-target.
- TargetFolate receptor alpha
Shares Mayo Clinic Comprehensive Cancer Center – 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.
- TargetNectin-4
Shares Overexpression, Mitosis & the spindle assembly checkpoint, Bispecific ADC, Bladder & urothelial cancer and the tag adc-target.
- TargetCD33
Shares Radio-antibody & radio-ADC, Antibody-drug conjugate (ADC) and the tag adc-target.
- TargetROR1
Shares Antibody-drug conjugate (ADC), Triple-negative breast cancer (TNBC) and the tag adc-target.