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TROP2 is a surface glycoprotein present at high levels on most epithelial cancers (breast, lung, urothelial, gastric, pancreatic) and at low levels on normal tissue. It does not drive the cancer; it is a delivery address, used by the approved ADCs sacituzumab govitecan and datopotamab deruxtecan and by sacituzumab tirumotecan, with a TROP2 PET tracer in development to pick patients. This dossier gathers the 31 products (3 approved), 181 trials, 2 pathways and 7 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Regulates calcium signalling and cell adhesion; overexpression correlates with shorter survival. 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.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Triple-negative breast cancer | 80-90% | IHC, any/moderate-high expression | ASCENT's exploratory biomarker analysis supported benefit in the high/medium H-score groups; the low-expression group was too small for definitive conclusions (290 of 468 assessable patients had TROP2 data). No TROP2 companion test is required for the breast-cancer indications. | 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 |
| Triple-negative breast cancer | 2.5-4.4% | Gene amplification (copy number) | Trop-2 expression was assessable in 290 of 468 ASCENT patients and sacituzumab govitecan benefit was seen at high and medium expression (progression-free survival 6.9 and 5.6 versus 2.5 and 2.2 months), with the low group too small to judge (Bardia 2021); cBioPortal: TACSTD2 amplification in the TNBC-filtered copy-number cohorts, 3 of 119, 2.5%, in brca_tcga_pan_can_atlas_2018 and 14 of 320, 4.4%, in brca_metabric; no TACSTD2 mutation in either. | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Approved | Phase 3 | Phase 2 | Phase 1 | Preclinical | Withdrawn or failed |
|---|---|---|---|---|---|---|
| ADC 27 | ||||||
| Cell therapy 3 | - | - | - | - | - | |
| Bispecific ADC 1 | - | - | - | - | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
ASCENT-03 NCT05382299 | 3 | Positive | First-line metastatic TNBC, not candidates for PD-1 inhibitors: sacituzumab govitecan vs chemotherapy | FDA reports 558 randomized patients with previously untreated unresectable locally advanced or metastatic TNBC who were not candidates for PD-1/PD-L1 therapy. Sacituzumab govitecan versus chemotherapy improved median PFS, 9.7 versus 6.9 months (HR 0.62, 95% CI 0.50 to 0.77). Overall survival was immature at approval. ClinicalTrials.gov lists 623 actual participants; the difference from the FDA efficacy-study population is retained without inventing a reconciliation. These are advanced-disease outcomes, not postoperative recurrence prevention. | |
ASCENT-04 / KEYNOTE-D19 NCT05382286 | 3 | Positive | First-line PD-L1+ (CPS ≥10) metastatic TNBC: sacituzumab govitecan + pembrolizumab vs chemotherapy + pembrolizumab | FDA reports 443 randomized patients with previously untreated advanced TNBC and PD-L1 CPS at least 10. Sacituzumab govitecan plus pembrolizumab versus chemotherapy plus pembrolizumab improved median PFS, 11.2 versus 7.8 months (HR 0.65, 95% CI 0.51 to 0.84). Overall survival was immature at approval. The June 24, 2026 approval concerns advanced disease, not postoperative recurrence prevention. | |
| 3 | Active | Open-Label, Global, Multicenter, Randomized, Phase 3 Study of Sacituzumab Govitecan Versus Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Progression on or After Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Immunotherapy | - | ||
TROPION-Breast02 NCT05374512 | 3 | Positive | First-line metastatic TNBC, not candidates for PD-1/PD-L1: Dato-DXd vs chemotherapy | TROPION-Breast02 randomized 644 patients (323/321) with previously untreated advanced TNBC for whom PD-1/PD-L1 inhibitor therapy was unsuitable. FDA reports median PFS 10.8 versus 5.6 months (HR 0.57, 95% CI 0.47 to 0.69) and OS 23.7 versus 18.7 months (HR 0.79, 95% CI 0.64 to 0.98). FDA approved the advanced-disease indication May 22, 2026. These outcomes do not establish postoperative benefit or provide a head-to-head comparison against sacituzumab govitecan. | |
TROPION-Breast01 NCT05104866 | 3 | Mixed | HR+/HER2- metastatic breast cancer after endocrine and 1-2 chemotherapies: Dato-DXd vs chemotherapy | PFS HR 0.63; OS HR 1.01. | |
TROPION-Lung01 NCT04656652 | 3 | Mixed | Previously treated advanced NSCLC: Dato-DXd vs docetaxel | PFS HR 0.75; OS HR 0.94. | |
TROPiCS-02 NCT03901339 | 3 | Positive | HR+/HER2- metastatic breast cancer after endocrine therapy, CDK4/6, and 2-4 chemotherapies: sacituzumab govitecan vs chemotherapy | OS 14.4 vs 11.2 months, HR 0.79. | |
ASCENT NCT02574455 | 3 | Positive | Pretreated metastatic TNBC: sacituzumab govitecan vs chemotherapy | OS 12.1 vs 6.7 months, HR 0.48. | |
| 3 | Recruiting | A Phase 3, Randomized, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab With or Without Bevacizumab Compared With Standard of Care as Firstline Maintenance Treatment for Participants With Persistent, Recurrent, or Newly Diagnosed Metastatic Cervical Cancer With PD-L1 CPS Greater Than or Equal to 1 (TroFuse-036/GOG-3123/ENGOT-cx22) | - | ||
| 3 | Recruiting | A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032) | - | ||
| 3 | Recruiting | A Phase 3, Randomized, Open-label, Multicenter Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) Maintenance Treatment With or Without Bevacizumab Versus Standard of Care in Participants With Newly Diagnosed Advanced Non-HRD Positive Ovarian Cancer Following First-line Platinum-based Chemotherapy (TroFuse-021/ENGOTov85/GOG-3102) | - | ||
| 3 | Recruiting | A Phase 3, Randomized, Open-label Study of Sacituzumab Tirumotecan (MK-2870) Versus Investigator's Choice of Non-platinum Chemotherapy in Participants With Pretreated Locally Advanced/Metastatic Urothelial Carcinoma | - | ||
| 3 | Active | A Phase III Randomised Study to Evaluate Dato-DXd and Durvalumab for Neoadjuvant/Adjuvant Treatment of Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer | - | ||
| 3 | Recruiting | A Open-label, Randomized, Multicenter Phase III Study of ESG401 Versus Investigator's Choice Chemotherapy in Patients With Locally Advanced or Metastatic HR+/HER2- Breast Cancer Who Had Failed at Least One Line of Chemotherapy | - | ||
| 3 | Recruiting | A Randomized, Open-label, Phase III Study of ESG401 Versus Investigator's Choice Chemotherapy as First-line Treatment in Patients With Unresectable Recurrent or Metastatic Triple-Negative Breast Cancer | - | ||
| 3 | Recruiting | A Phase III Study of JSKN016 Versus Treatment of Physician's Choice in Patients With Triple-Negative Breast Cancer Who Have Failed Standard of Care | - | ||
| 3 | Active | A Randomized, Open-Label, Multicenter Phase 3 Study to Evaluate SKB264 Monotherapy Versus Pemetrexed in Combination With Platinum in Patients With Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer With EGFR Mutation Who Have Failed to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Therapy | - | ||
| 3 | Active | A Phase III, Randomised Study of Adjuvant Dato-DXd in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Standard of Care, Following Complete Tumour Resection, in Participants With Stage I Adenocarcinoma NSCLC Who Are ctDNA-positive or Have High-risk Pathological Features | - | ||
| 3 | Recruiting | A Study of Sacituzumab Tirumotecan (MK-2870) as a Single Agent and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer (MK-2870-010) | - | ||
| 3 | Recruiting | A Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Triple-Negative Breast Cancer (MK-2870-011/TroFuse-011) | - | ||
| 3 | Active | A Randomized, Open-Label, Multicenter, Phase III Clinical Study of SKB264 in Combination With Osimertinib Versus Osimertinib Alone as First-Line Treatment for Patients With Epidermal Growth Factor Receptor (EGFR) Mutations, Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer | - | ||
| 3 | Active | A Randomized, Open-Label, Multicenter Phase 3 Clinical Study of SKB264 in Combination With Pembrolizumab Versus Chemotherapy in Combination With Pembrolizumab as First-Line Treatment for PD-L1 Negative Patients With Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer | - | ||
| 3 | Active | A Randomized, Open-Label, Multicenter Phase III Clinical Study of SKB264 in Combination With Pembrolizumab Versus Pembrolizumab as First-Line Treatment for PD-L1 Positive Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer | - | ||
| 3 | Recruiting | A Study to Assess Efficacy and Safety of Pembrolizumab With or Without Sacituzumab Tirumotecan (MK- 2870) in Adult Participants With Resectable Non Small Cell Lung Cancer (NSCLC) Not Achieving Pathological Complete Response (pCR) (MK-2870-019) | - | ||
| 3 | Recruiting | A Phase 3 Randomized, Open-label, Multicenter Study to Compare the Efficacy and Safety of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in Combination With Pembrolizumab Versus Pembrolizumab Alone as First-line Maintenance Treatment in Participants With Mismatch Repair Proficient Endometrial Cancer (TroFuse-033/GOG-3119/ENGOT-en29) | - | ||
| 3 | Active | A Phase 3 Randomized, Active-controlled, Open-label, Multicenter Study to Compare the Efficacy and Safety of MK-2870 Monotherapy Versus Treatment of Physician's Choice as Second-line Treatment for Participants With Recurrent or Metastatic Cervical Cancer (TroFuse-020/GOG-3101/ENGOT-cx20) | - | ||
| 3 | Active | A Phase 3, Multicenter, Open-label, Randomized Study to Compare the Efficacy and Safety of MK-2870 Versus Treatment of Physician's Choice in 3L+ Advanced/Metastatic Gastroesophageal Adenocarcinoma (Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, and Esophageal Adenocarcinoma) | - | ||
| 3 | Recruiting | A Phase 3, Randomized, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of Sacituzumab Tirumotecan Maintenance Treatment With or Without Bevacizumab Versus Standard of Care After Second-line Platinum-based Doublet Chemotherapy in Participants With Platinum-sensitive Recurrent Ovarian Cancer (TroFuse-022/ENGOT-ov84/GOG-3103) | - | ||
| 3 | Recruiting | A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer | - | ||
| 3 | Recruiting | Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy (ASCENT-05/AFT-65 OptimICE-RD/GBG 119/NSABP B-63) | - |
Mutation of the cysteine that osimertinib binds covalently; abolishes drug binding while EGFR stays active.
TOP1 mutations (e.g., E418K) or reduced expression prevent trapping of the cleavage complex.
Schlafen-11 is required for replication-stress-induced death; its epigenetic silencing confers resistance to TOP1 (and platinum) agents.
SN-38 is an ABCG2 substrate; DXd and MMAE are ABCB1 substrates; mesenchymal states upregulate both.
Reduced HER2 or TROP2 surface expression after treatment; less frequent than payload resistance for HER2-low disease.
Defective endocytosis or lysosomal cathepsin activity limits payload release.
Without RB, CDK4/6 inhibition cannot arrest the cell cycle.
Before a cell divides it must copy three billion letters of DNA exactly once, 'licensing' thousands of start points in advance and firing them in waves. Cancers driven by MYC, cyclin E or RAS fire excess start points too fast, and antimetabolites such as 5-FU, topoisomerase poisons such as irinotecan and platinum drugs all jam this copying machinery.
Which nodes have drugs →Cancer cells can install pumps in their outer membrane that throw chemotherapy back out as fast as it comes in. The same pumps guard the gut, brain and bone marrow in healthy tissue, which is why blocking them failed as a strategy and why drug designers now choose payloads the pumps cannot grip.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
| Cell line | Identifiers | Why it is used |
|---|---|---|
| MDA-MB-468 | CVCL_0419 · ACH-000849 | TROP2-high TNBC. |
| HCC1806 | CVCL_1258 · ACH-000624 | TROP2-high TNBC. |
| BxPC-3 | CVCL_0186 · ACH-000535 | TROP2-high pancreatic. |
| NCI-H1975 | CVCL_1511 · ACH-000587 | TROP2-positive lung; Dato-DXd model. |
| Calu-3 | CVCL_0609 · ACH-000392 | TROP2-positive lung. |
| MDA-MB-231 | CVCL_0062 · ACH-000768 | TROP2-low comparator. |
Why unresolved. TROP2 ADCs are given without testing because IHC did not separate responders in ASCENT or TROPION-Breast01; TROPION-Lung01 reported a computational membrane-ratio score retrospectively but it is unvalidated.
What would answer it. Prospective validation of a quantitative TROP2 score or a TROP2 PET tracer against progression-free survival in a randomised ADC trial.
Query 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.
The dossier as machine-readable JSON, at /api/v1/dossiers/trop2.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/trop2.json. Licence CC BY-NC 4.0.