{"entity":{"id":"top1","kind":"target","name":"Topoisomerase I (TOP1)","aka":[],"tldr":"The enzyme that nicks one DNA strand to relieve twisting while DNA is copied. Camptothecins and the payloads of several antibody-drug conjugates trap it on the DNA so the nick becomes a permanent break when the cell replicates.","summary":"Topoisomerase I relaxes supercoiled DNA by cutting one strand, letting it rotate and resealing it. Camptothecin derivatives such as irinotecan, topotecan, SN-38, DXd and exatecan bind the enzyme-DNA complex and stop the reseal step, so replication forks collide with the trapped complex and create double-strand breaks. The same chemistry is the payload of sacituzumab govitecan, trastuzumab deruxtecan and datopotamab deruxtecan, which explains their shared toxicities of neutropenia and diarrhoea and the cross-resistance seen when one topoisomerase I antibody-drug conjugate follows another.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/TOP1","links":[{"label":"UniProt P11387: TOP1","url":"https://www.uniprot.org/uniprotkb/P11387/entry"}],"tags":[],"related":[],"cancers":["colorectal","sclc","tnbc","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["irinotecan","topotecan","sacituzumab-govitecan","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06797999"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"TOP1","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"many-types","tumourAgnostic":true,"specificityNote":"Broadly expressed or essential: HPA lists TOP1 among essential proteins and finds the RNA at low tissue specificity; the 4 medicines aimed at it (Irinotecan (and liposomal irinotecan), Topotecan, Sacituzumab govitecan and more) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA TOP1: RNA low tissue specificity; high antibody staining in 27 normal tissues; highest cancer staining head and neck cancer (4 of 4 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Lung cancer (all types), Breast cancer (all types)); approvals of single-target medicines aimed at it also list Bladder & urothelial cancer, Gastric & gastro-oesophageal junction cancer, Oesophageal cancer, Salivary gland cancers and more, not counted; Open Targets associates it with 7 specific cancer types at or above 0.5 (small cell lung carcinoma, breast cancer, non-small cell lung carcinoma, cervical cancer, colorectal cancer, ovarian cancer and more). Tissue-agnostic: Trastuzumab deruxtecan US 2024: \"HER2 IHC3+ solid tumours (tumour-agnostic)\". (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas TOP1 tissue","url":"https://www.proteinatlas.org/ENSG00000198900-TOP1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000198900 associations","url":"https://platform.opentargets.org/target/ENSG00000198900/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11986","ensembl":"ENSG00000198900","uniprot":"P11387","entrez":"7150","firstDescribed":1988,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: D'Arpa et al, Proc. Natl. Acad. Sci. U.S.A, 1988, \"cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2833744/","biology":"Type IB topoisomerase that relieves torsional stress during replication and transcription; trapped as a covalent cleavage complex by camptothecins.","whereFound":["Expressed in all dividing cells; relevant wherever camptothecin or topoisomerase I payload drugs are used"],"targetClass":"enzyme","prevalence":[{"cancerId":"metastatic-cancer","pct":"all","measure":"Housekeeping enzyme present in every dividing cell (DNA unwinding during replication); not a selection marker, which is why these drugs are given by cancer type rather than by test."}]},"route":"/targets/top1/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"drug":[{"id":"hr070803","kind":"drug","name":"HR070803","route":"/drugs/hr070803/"},{"id":"irinotecan","kind":"drug","name":"Irinotecan (and liposomal irinotecan)","route":"/drugs/irinotecan/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"topotecan","kind":"drug","name":"Topotecan","route":"/drugs/topotecan/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"trial":[{"id":"nct06797999","kind":"trial","name":"First-in-Human Study of ADCE-D01 in Soft Tissue Sarcoma","route":"/trials/nct06797999/"}],"target":[{"id":"b7h4","kind":"target","name":"B7-H4 (VTCN1)","route":"/targets/b7h4/"}]}}