{"entity":{"id":"trop2","kind":"target","name":"TROP2","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-04","links":[{"label":"UniProt P09758: TACSTD2 (TROP2)","url":"https://www.uniprot.org/uniprotkb/P09758/entry"}],"tags":["adc-target","pet-target"],"related":["trop2-expression"],"cancers":["tnbc","breast-hr-positive","nsclc","urothelial"],"sections":[],"technologies":[],"targets":[],"drugs":["ak146d1","bio-106","datopotamab-deruxtecan","eb-nk-301","lcb84","sacituzumab-govitecan","sacituzumab-tirumotecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07299747"],"people":[],"bottlenecks":[],"keyPapers":["paper-bardia-ascent-trop2-biomarker-ann-oncol-2021"],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer: sacituzumab govitecan benefit was seen at high and medium Trop-2 H-score in ASCENT with a low group too small to judge (Bardia 2021); no label requires the test. TACSTD2 amplification is rare, 2.5 to 4.4% (cBioPortal)."],"symbol":"TACSTD2","role":[],"sources":[],"specificity":"tumour-associated","distribution":"few-types","specificityNote":"Tumour-associated overexpression: 6 cell-killing or cell-finding medicines (AK146D1, BIO-106, Datopotamab deruxtecan and more) aim at the antigen, which HPA finds stained high in 1 normal tissue; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA TACSTD2: RNA tissue enhanced (esophagus 1,245 nTPM, salivary gland 585 nTPM, skin 1 555 nTPM); blood lineage group enriched (dendritic cells 4 nTPM, granulocytes 15 nTPM, monocytes 4 nTPM); high antibody staining in 1 normal tissue; highest cancer staining urothelial cancer (1 of 11 high). Distribution: 4 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Lung cancer (all types), Bladder & urothelial cancer, Pancreatic ductal adenocarcinoma); approvals of single-target medicines aimed at it also list Endometrial cancer, Cervical cancer, not counted; Open Targets associates it with 3 specific cancer types at or above 0.5 (breast cancer, non-small cell lung carcinoma, triple-negative breast carcinoma). (Rule 5 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas TACSTD2 tissue","url":"https://www.proteinatlas.org/ENSG00000184292-TACSTD2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas TACSTD2 pathology","url":"https://www.proteinatlas.org/ENSG00000184292-TACSTD2/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000184292 associations","url":"https://platform.opentargets.org/target/ENSG00000184292/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11530","ensembl":"ENSG00000184292","uniprot":"P09758","entrez":"4070","firstDescribed":1989,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Linnenbach A.J. et al, Proc. Natl. Acad. Sci. U.S.A, 1989, \"Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2911574/","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.","whereFound":["Triple-negative breast cancer (~80-90% express)","HR+ breast cancer","NSCLC","Urothelial carcinoma","Gastric, pancreatic, endometrial cancers","Triple-negative breast cancer: protein expression (h-score) and amplification 2-4%"],"targetClass":"surface-antigen","prevalence":[{"cancerId":"tnbc","pct":"80-90","measure":"IHC, any/moderate-high expression","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13059868/","note":"ASCENT benefit was independent of TROP2 IHC level"},{"cancerId":"breast-hr-positive","pct":"75-90","measure":"IHC, any expression","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13059868/"},{"cancerId":"nsclc","pct":"60-70","measure":"IHC, moderate-high","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13059868/","note":"Adenocarcinoma and squamous"},{"cancerId":"urothelial","pct":"80-90","measure":"IHC, any expression","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13059868/"},{"cancerId":"pancreatic","pct":50,"measure":"IHC, any expression","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13059868/","note":"Approximate; heterogeneous"},{"cancerId":"tnbc","pct":"2-4","measure":"Protein expression (H-score) and amplification","source":"https://doi.org/10.1016/j.annonc.2021.06.002","note":"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."}]},"route":"/targets/trop2/","neighbours":{"biomarker":[{"id":"trop2-expression","kind":"biomarker","name":"TROP2 expression","route":"/biomarkers/trop2-expression/"}],"cancer":[{"id":"lung-adenocarcinoma","kind":"cancer","name":"Adenocarcinoma of the lung","route":"/cancers/lung-adenocarcinoma/"},{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pdl1-high-nsclc","kind":"cancer","name":"PD-L1-high non-small-cell lung cancer without a driver mutation","route":"/cancers/pdl1-high-nsclc/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"drug":[{"id":"ak146d1","kind":"drug","name":"AK146D1","route":"/drugs/ak146d1/"},{"id":"bio-106","kind":"drug","name":"BIO-106","route":"/drugs/bio-106/"},{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"eb-nk-301","kind":"drug","name":"EB-NK-301","route":"/drugs/eb-nk-301/"},{"id":"lcb84","kind":"drug","name":"LCB84","route":"/drugs/lcb84/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"sacituzumab-tirumotecan","kind":"drug","name":"Sacituzumab tirumotecan","route":"/drugs/sacituzumab-tirumotecan/"}],"trial":[{"id":"ascent","kind":"trial","name":"ASCENT","route":"/trials/ascent/"},{"id":"nct07299747","kind":"trial","name":"Clinical Trial of VBC103 in Patients With Advanced Malignant Solid Tumors","route":"/trials/nct07299747/"},{"id":"diamond","kind":"trial","name":"DIAMOND","route":"/trials/diamond/"},{"id":"tropics-02","kind":"trial","name":"TROPiCS-02","route":"/trials/tropics-02/"},{"id":"tropion-lung05","kind":"trial","name":"TROPION-Lung05","route":"/trials/tropion-lung05/"}],"paper":[{"id":"paper-ascent-nejm-2021","kind":"paper","name":"ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer","route":"/key-papers/paper-ascent-nejm-2021/"},{"id":"paper-bardia-ascent-trop2-biomarker-ann-oncol-2021","kind":"paper","name":"Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer","route":"/key-papers/paper-bardia-ascent-trop2-biomarker-ann-oncol-2021/"},{"id":"paper-asco-biomarkers-metastatic-breast-cancer-guideline-jco-2022","kind":"paper","name":"Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update","route":"/key-papers/paper-asco-biomarkers-metastatic-breast-cancer-guideline-jco-2022/"},{"id":"paper-tropion-breast02-ann-oncol-2026","kind":"paper","name":"Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial","route":"/key-papers/paper-tropion-breast02-ann-oncol-2026/"},{"id":"paper-tropion-breast01-jco-2024","kind":"paper","name":"TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival","route":"/key-papers/paper-tropion-breast01-jco-2024/"}],"term":[{"id":"antigen","kind":"term","name":"Antigen","route":"/terms/antigen/"},{"id":"her2-low-and-trop2-adc-eligibility-tnbc","kind":"term","name":"HER2-low eligibility for trastuzumab deruxtecan, and TROP2 ADCs without a test (triple-negative disease)","route":"/terms/her2-low-and-trop2-adc-eligibility-tnbc/"},{"id":"overexpression","kind":"term","name":"Overexpression","route":"/terms/overexpression/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"},{"id":"trop2-adc-roadmap","kind":"roadmap","name":"TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET","route":"/roadmaps/trop2-adc-roadmap/"}],"idea":[{"id":"idea-tnbc-adc-sequencing-trial","kind":"idea","name":"A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer","route":"/ideas/idea-tnbc-adc-sequencing-trial/"},{"id":"idea-alpha-after-adc","kind":"idea","name":"Alpha radioligands after ADC failure","route":"/ideas/idea-alpha-after-adc/"},{"id":"idea-bio2-myeloid-engager-bispecific","kind":"idea","name":"Bispecific antibodies that engage macrophages instead of T cells","route":"/ideas/idea-bio2-myeloid-engager-bispecific/"},{"id":"idea-dual-payload-first","kind":"idea","name":"Dual-payload ADCs in first line to prevent resistance","route":"/ideas/idea-dual-payload-first/"},{"id":"idea-bio1-antigen-mapping-at-progression","kind":"idea","name":"Re-map the tumour's surface proteins before choosing the next antibody drug","route":"/ideas/idea-bio1-antigen-mapping-at-progression/"},{"id":"idea-fund-benefit-indexed-exclusivity","kind":"idea","name":"Shorter exclusivity for later-in-class drugs without added benefit","route":"/ideas/idea-fund-benefit-indexed-exclusivity/"},{"id":"idea-trop2-pet-selection","kind":"idea","name":"TROP2 PET to choose and sequence TROP2 ADCs","route":"/ideas/idea-trop2-pet-selection/"},{"id":"idea-bio2-transferrin-shuttle-adc","kind":"idea","name":"Use the brain's own transport door to carry antibody drugs across","route":"/ideas/idea-bio2-transferrin-shuttle-adc/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"bispecific-adc","kind":"technology","name":"Bispecific ADC","route":"/technologies/bispecific-adc/"},{"id":"immuno-pet","kind":"technology","name":"Immuno-PET","route":"/technologies/immuno-pet/"},{"id":"trop2-pet","kind":"technology","name":"TROP2 PET","route":"/technologies/trop2-pet/"}],"company":[{"id":"avenzo","kind":"company","name":"Avenzo Therapeutics","route":"/companies/avenzo/"},{"id":"pathos-ai","kind":"company","name":"Pathos AI","route":"/companies/pathos-ai/"}],"institution":[{"id":"fuscc","kind":"institution","name":"Fudan University Shanghai Cancer Center","route":"/institutions/fuscc/"}],"pathway":[{"id":"dna-replication-licensing","kind":"pathway","name":"DNA replication & origin licensing","route":"/pathways/dna-replication-licensing/"},{"id":"drug-efflux-pumps","kind":"pathway","name":"Drug efflux pumps (ABC transporters)","route":"/pathways/drug-efflux-pumps/"},{"id":"emt","kind":"pathway","name":"Epithelial-mesenchymal transition & drug efflux","route":"/pathways/emt/"}],"pairing":[{"id":"trop2-pet-to-adc","kind":"pairing","name":"TROP2 PET → TROP2 ADC selection","route":"/pairings/trop2-pet-to-adc/"}],"person":[{"id":"aditya-bardia","kind":"person","name":"Aditya Bardia","route":"/people/aditya-bardia/"},{"id":"xu-binghe","kind":"person","name":"Binghe Xu","route":"/people/xu-binghe/"},{"id":"hope-rugo","kind":"person","name":"Hope S. Rugo","route":"/people/hope-rugo/"},{"id":"sohn-joohyuk","kind":"person","name":"Joohyuk Sohn","route":"/people/sohn-joohyuk/"},{"id":"sara-tolaney","kind":"person","name":"Sara M. Tolaney","route":"/people/sara-tolaney/"},{"id":"song-shaoli","kind":"person","name":"Shaoli Song","route":"/people/song-shaoli/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-incentive-misalignment","kind":"bottleneck","name":"Incentives reward me-too drugs and marginal gains","route":"/bottlenecks/b-incentive-misalignment/"}]}}