TROP2
A protein that sits on the outside of many cancer cells far more than on normal cells, making it a good address for delivering drugs.
Trophoblast cell-surface antigen 2 is a transmembrane glycoprotein overexpressed in most epithelial cancers (breast, lung, urothelial, gastric, pancreatic) with low normal-tissue expression. It is not an oncogenic driver; it is a delivery address. Three TROP2 ADCs are approved or in registration (sacituzumab govitecan, datopotamab deruxtecan, sacituzumab tirumotecan) and a TROP2 PET tracer is in development to select patients.
- 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 protein that sits on the outside of many cancer cells far more than on normal cells, making it a good address for delivering drugs.
- 1 · What it is
A protein that sits on the outside of many cancer cells far more than on normal cells, making it a good address for delivering drugs.
- 2 · What goes wrong in cancer
Regulates calcium signalling and cell adhesion; overexpression correlates with poor prognosis. Expression is heterogeneous within tumours, which limits the value of IHC selection.
- 3 · How drugs use it
4 products aim at TROP2: antibody-drug conjugates. 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
Regulates calcium signalling and cell adhesion; overexpression correlates with poor prognosis. Expression is heterogeneous within tumours, which limits the value of IHC selection. Internalises on antibody binding and traffics to lysosomes, which is what makes it a good ADC target.
- Triple-negative breast cancer (~80-90% express)
- HR+ breast cancer
- NSCLC
- Urothelial carcinoma
- Gastric, pancreatic, endometrial cancers
How common it is, by cancer
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Triple-negative breast cancer | 80-90% | IHC, any/moderate-high expression | ASCENT benefit was independent of TROP2 IHC level | PMC |
| Bladder & urothelial cancer | 80-90% | IHC, any expression | PMC | |
| HR-positive / HER2-negative breast cancer | 75-90% | IHC, any expression | PMC | |
| Non-small-cell lung cancer | 60-70% | IHC, moderate-high | Adenocarcinoma and squamous | PMC |
| Pancreatic ductal adenocarcinoma | 50% | IHC, any expression | Approximate; heterogeneous | PMC |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
AK146D1 is Akeso's Nectin-4 × TROP2 bispecific ADC, combining the two most validated ADC addresses in one molecule.
Datopotamab deruxtecan (Datroway) is the second TROP2 ADC and shares Enhertu's payload. In 2026 it became a first-line option for triple-negative breast cancer patients who cannot receive immunotherapy.
The first TROP2-targeted ADC. It delivers a strong chemotherapy directly to breast and bladder cancer cells and is now a first-line option in triple-negative breast cancer.
Sacituzumab tirumotecan is a third TROP2 ADC from China, licensed to Merck for a very large global programme. It is approved in China; in the US it has a priority voucher but not yet approval.
For hormone-receptor-positive metastatic breast cancer that has already had chemotherapy, Dato-DXd controls the disease for longer with fewer severe side effects than chemotherapy, but does not help patients live longer, so it is not a standard option here. The result is a reminder that progression-free survival is a surrogate; regulators and clinicians should wait for survival data before adopting an ADC in a setting where later therapies are effective.
Sacituzumab govitecan is a standard second-line or later treatment for metastatic triple-negative breast cancer, roughly doubling survival compared with the chemotherapies it was tested against. Patients should expect neutropenia and diarrhoea, which are manageable with growth factor support and loperamide. Trials are now testing it earlier, in first-line combinations with pembrolizumab and after surgery for residual disease.
Latest papers
topQuery for this target: (TITLE:"TROP2" OR ABSTRACT:"TROP2" OR TITLE:"TACSTD2" OR ABSTRACT:"TACSTD2") 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 TROP2, not a curated reading list.
Pages like this
not linked directly; found by shared links- TargetNectin-4
Shares Avenzo Therapeutics, Overexpression, AK146D1, Bispecific ADC and the tag adc-target.
- TargetB7-H3
Shares Alpha radioligands after ADC failure, Overexpression, Re-map the tumour's surface proteins before choosing the next antibody drug, Bispecific ADC and the tag adc-target.
- TargetFolate receptor alpha
Shares Re-map the tumour's surface proteins before choosing the next antibody drug, Endometrial cancer, Antibody-drug conjugate (ADC), Triple-negative breast cancer (TNBC) and the tag adc-target.
- TargetHER2
Shares Alpha radioligands after ADC failure, Bispecific antibodies that engage macrophages instead of T cells, Dual-payload ADCs in first line to prevent resistance, Joohyuk Sohn and the tag adc-target.
- TargetTissue factor
Shares Cervical cancer, 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.
- TargetCD123
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
- TargetCD33
Shares Antibody-drug conjugate (ADC) and the tag adc-target.