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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 7 products (3 approved), 134 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 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 |
| Triple-negative breast cancer | 2-4% | Protein expression (H-score) and amplification | 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 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. | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Approved | Phase 2 | Phase 1 |
|---|---|---|---|
| ADC 4 | - | ||
| Antibody 1 | - | - | |
| Bispecific ADC 1 | - | - | |
| Cell therapy 1 | - | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
ASCENT-03 NCT05382299 | 3 | Positive | First-line metastatic TNBC, not candidates for PD-1 inhibitors: sacituzumab govitecan vs chemotherapy | PFS HR 0.62. | |
ASCENT-04 / KEYNOTE-D19 NCT05382286 | 3 | Positive | First-line PD-L1+ (CPS ≥10) metastatic TNBC: sacituzumab govitecan + pembrolizumab vs chemotherapy + pembrolizumab | PFS HR 0.65; PFS2 improved. | |
| 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 | OS 23.7 vs 18.7 months; PFS also improved. | |
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 Phase 3, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Sac-TMT (Sacituzumab Tirumotecan, MK-2870) Followed by Carboplatin/Paclitaxel vs Chemotherapy, Both in Combination With Pembrolizumab as Neoadjuvant Therapy for High-Risk, Early-Stage, Triple-Negative Breast Cancer or Hormone Receptor-low Positive/Human Epidermal Growth Factor Receptor-2 Negative Breast Cancer | - | ||
| 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 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, Open-label, Global Study of Adjuvant Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Standard of Care, Following Complete Tumour Resection, in Participants With Stage I Adenocarcinoma Non-small Cell Lung Cancer Who Are ctDNA-positive or Have High-risk Pathological Features (TROPION-Lung12) | - | ||
| 3 | Recruiting | An Open-label, Randomized Phase 3 Study of MK-2870 as a Single Agent and in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer | - | ||
| 3 | Recruiting | A Phase 3, Randomized, Open-label Study Comparing Efficacy and Safety of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) as a Monotherapy and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice in Participants With Previously Untreated Locally Recurrent Unresectable or Metastatic Triple-Negative Breast Cancer Expressing PD-L1 at CPS Less Than 10 (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 Phase 3 Randomized Open-Label Study of Adjuvant Pembrolizumab With or Without MK-2870 in Participants With Resectable Stage II to IIIB (N2) NSCLC Not Achieving pCR After Receiving Neoadjuvant Pembrolizumab With Platinum-based Doublet Chemotherapy Followed by Surgery | - | ||
| 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 Phase III, Open-label, Sponsor-blind, Randomized Study of Dato-DXd With or Without Osimertinib Versus Platinum-based Doublet Chemotherapy for Participants With EGFR-mutated Locally Advanced or Metastatic Non-small Cell Lung Cancer Whose Disease Has Progressed on Prior Osimertinib Treatment (TROPION-Lung15) | - | ||
| 3 | Recruiting | Stage II to III TNBC with residual invasive disease after neoadjuvant therapy and surgery: adjuvant sacituzumab govitecan + pembrolizumab vs pembrolizumab ± capecitabine | - | ||
| 3 | Active | A Phase 3 Asian Study of Sacituzumab Govitecan (IMMU-132) Versus Treatment of Physician's Choice (TPC) in Subjects With Hormonal Receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (MBC) Who Have Failed at Least 2 Prior Chemotherapy Regimens | - | ||
| 3 | Active | A Randomized Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in Subjects With No Prior Therapy for Advanced or Metastatic PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung07) | - | ||
| 3 | Recruiting | NeoAdjuvant Dynamic Marker - Adjusted Personalized Therapy Comparing Sacituzumab Govitecan Versus Sacituzumab Govitecan+Pembrolizumab in Low-risk, Triple-negative Early Breast Cancer (ADAPT-TN-III) | - | ||
| 3 | Planned | NeoAdjuvant Dynamic Marker - Adjusted Personalized Therapy Comparing Sacituzumab Govitecan+Pembrolizumab vs. SoC Chemotherapy in Clinical Stage II-III, Triple-negative Early Breast Cancer | - |
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.