{"entity":{"id":"muc16","kind":"target","name":"MUC16 (CA-125)","aka":[],"tldr":"The giant mucin that is shed into blood as the CA-125 ovarian cancer marker; its membrane stalk is being targeted by ADCs and T-cell engagers.","summary":"MUC16 is a giant transmembrane mucin overexpressed in ovarian (~80%), pancreatic, endometrial and lung cancers; its shed ectodomain is CA-125, used since 1983 for monitoring ovarian cancer. Therapeutics target the membrane-retained stalk: ubamatamab (MUC16×CD3 bispecific, Regeneron) in phase 2 in ovarian cancer, sofituzumab vedotin (ADC) discontinued, MUC16 CAR-T (with IL-12 armouring) in phase 1. Anti-CA-125 vaccines (abagovomab, oregovomab) failed in phase 3, oregovomab most recently in 2024 (FLORA-5).","asOf":"2026-09-21","wikipedia":"https://en.wikipedia.org/wiki/CA-125","links":[{"label":"Ubamatamab phase 1/2 study design (JCO 2024, TPS5632)","url":"https://doi.org/10.1200/JCO.2024.42.16_suppl.TPS5632"},{"label":"Ubamatamab translational study (Zhu et al., Clin Transl Sci 2024)","url":"https://doi.org/10.1111/cts.70082"}],"tags":["gap-fill"],"related":["mesothelin","folr1"],"cancers":["ovarian","pancreatic","endometrial"],"sections":[],"technologies":["t-cell-engager","adc","car-t"],"targets":[],"drugs":["ubamatamab"],"companies":["regeneron"],"institutions":[],"pathways":[],"terms":["ca-125"],"trials":["nct07480954"],"people":[],"bottlenecks":[],"keyPapers":["paper-zhu-clin-transl-sci"],"journals":[],"dependsOn":[],"notes":[],"symbol":"MUC16","role":[],"sources":[],"specificity":"tumour-associated","distribution":"few-types","specificityNote":"Tumour-associated overexpression: 1 cell-killing or cell-finding medicine (Ubamatamab) aim at the antigen, which HPA finds stained high in 4 normal tissues; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA MUC16: RNA group enriched (adipose tissue 7 nTPM, cervix 15 nTPM, fallopian tube 6 nTPM); high antibody staining in 4 normal tissues; highest cancer staining ovarian cancer (11 of 11 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Ovarian cancer, Pancreatic ductal adenocarcinoma, Endometrial cancer); Open Targets associates it with 1 specific cancer type at or above 0.5 (ovarian cancer). (Rule 5 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas MUC16 tissue","url":"https://www.proteinatlas.org/ENSG00000181143-MUC16/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas MUC16 pathology","url":"https://www.proteinatlas.org/ENSG00000181143-MUC16/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000181143 associations","url":"https://platform.opentargets.org/target/ENSG00000181143/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:15582","ensembl":"ENSG00000181143","uniprot":"Q8WXI7","entrez":"94025","firstDescribed":2001,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: O'Brien T.J. et al, Tumor Biol, 2001, \"The CA 125 gene: an extracellular superstructure dominated by repeat sequences\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/11786729/","biology":"22,000-amino-acid mucin with tandem repeats, SEA domains cleaved to release CA-125, and a short cytoplasmic tail; mediates immune evasion (binds Siglec-9, mesothelin), adhesion to mesothelium and metastasis.","whereFound":["High-grade serous ovarian cancer (~80%)","Pancreatic adenocarcinoma (~65%)","Endometrial, lung adenocarcinoma, mesothelioma","Serum CA-125 in ovarian cancer monitoring"],"targetClass":"surface-antigen","prevalence":[{"cancerId":"ovarian","pct":"80","measure":"MUC16 expression","source":"https://doi.org/10.1158/1078-0432.CCR-06-1707"}]},"route":"/targets/muc16/","neighbours":{"target":[{"id":"folr1","kind":"target","name":"Folate receptor alpha","route":"/targets/folr1/"},{"id":"mesothelin","kind":"target","name":"Mesothelin","route":"/targets/mesothelin/"}],"cancer":[{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"serum-tumour-markers","kind":"technology","name":"Serum tumour markers: proper use and misuse","route":"/technologies/serum-tumour-markers/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"drug":[{"id":"ubamatamab","kind":"drug","name":"Ubamatamab","route":"/drugs/ubamatamab/"}],"company":[{"id":"regeneron","kind":"company","name":"Regeneron","route":"/companies/regeneron/"}],"term":[{"id":"ca-125","kind":"term","name":"CA-125","route":"/terms/ca-125/"},{"id":"tumour-markers","kind":"term","name":"Tumour markers (CEA, LDH, chromogranin, thyroglobulin)","route":"/terms/tumour-markers/"}],"trial":[{"id":"nct07480954","kind":"trial","name":"Dual-Targeting CAR-NK Cells for Recurrent Ovarian Cancer (MSLN, FRα, MUC16)","route":"/trials/nct07480954/"}],"paper":[{"id":"paper-zhu-clin-transl-sci","kind":"paper","name":"Translational findings support regimen selection for first-in-human study of ubamatamab (MUC16 × CD3 bispecific antibody) in patients with recurrent ovarian cancer","route":"/key-papers/paper-zhu-clin-transl-sci/"}]}}