HER3

HER3 is a cousin of HER2 that cancers use as an escape route when HER2 or EGFR are blocked.

HER3 has weak kinase activity but is the preferred dimerisation partner of HER2 and a major driver of resistance to EGFR and HER2 inhibitors. Patritumab deruxtecan (HER3-DXd) and the EGFR×HER3 bispecific ADC izalontamab brengitecan make it a delivery target rather than a signalling target.

HER3: what it is and how drugs act on it · animated generic schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · HER3 is a cousin of HER2 that cancers use as an escape route when HER2 or EGFR are blocked.

1 · What it is
HER3 is a cousin of HER2 that cancers use as an escape route when HER2 or EGFR are blocked.
2 · What goes wrong in cancer
Neuregulin (NRG1) ligand; NRG1 fusions are rare drivers targeted by zenocutuzumab. Broadly expressed across breast, lung, and colorectal cancers.
3 · How drugs use it
4 products aim at HER3: antibodies, antibody-drug conjugates and bispecific antibodies. 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

Neuregulin (NRG1) ligand; NRG1 fusions are rare drivers targeted by zenocutuzumab. Broadly expressed across breast, lung, and colorectal cancers.

Where it is found

Breast cancer (all subtypes)
EGFR-mutant NSCLC
Colorectal
NRG1-fusion tumours

Class

surface antigen · ERBB3

How common it is, by cancer

Cancer	Prevalence	Measure	Note	Source
Non-small-cell lung cancer	80-90%	IHC, any expression	EGFR-mutant NSCLC in HERTHENA-Lung01	Wikipedia
Triple-negative breast cancer	50-70%	IHC, any expression		Wikipedia
HR-positive / HER2-negative breast cancer	50-70%	IHC, any expression		Wikipedia

Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.

Products

4top

Phase 3Bispecific ADC

Izalontamab brengitecan

Izalontamab brengitecan is the first bispecific ADC to succeed in a phase 3 trial, hitting two growth receptors at once in triple-negative breast cancer.

Phase 3ADC

Patritumab deruxtecan

A HER3-directed ADC with Enhertu's payload, active in lung and all subtypes of breast cancer, but with a bumpy regulatory road.

ApprovedMonoclonal antibody (anti-HER2, dimerisation domain)

Pertuzumab · Perjeta; Phesgo (with trastuzumab, subcutaneous)

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.

ApprovedBispecific antibody (HER2×HER3)

Zenocutuzumab · Bizengri

Zenocutuzumab is the first drug for cancers driven by NRG1 gene fusions, working by blocking HER3 from receiving its growth signal.