{"entity":{"id":"top2a","kind":"target","name":"Topoisomerase II alpha (TOP2A)","aka":[],"tldr":"The enzyme that cuts both DNA strands to untangle chromosomes before cell division. Etoposide and the anthracyclines hold it in the cut state, filling dividing cells with double-strand breaks.","summary":"Topoisomerase II alpha passes one DNA double helix through a transient break in another, decatenating replicated chromosomes and relaxing supercoils; its expression peaks in proliferating cells. Etoposide and anthracyclines such as doxorubicin stabilise the covalent enzyme-DNA complex, converting a normal catalytic step into lasting double-strand breaks. Etoposide is central to small-cell lung cancer, germ cell tumour and lymphoma regimens; anthracyclines to breast cancer, lymphoma and sarcoma regimens. Therapy-related leukaemia with KMT2A rearrangement and anthracycline cardiotoxicity are the class hazards.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/TOP2A","links":[{"label":"UniProt P11388: TOP2A","url":"https://www.uniprot.org/uniprotkb/P11388/entry"}],"tags":[],"related":[],"cancers":["sclc","testicular","dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":["etoposide","doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"TOP2A","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"Broadly expressed or essential: HPA lists TOP2A among essential proteins; the 8 medicines aimed at it (Etoposide, Doxorubicin, Aldoxorubicin 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 TOP2A: RNA tissue enhanced (lymphoid tissue 119 nTPM, testis 62 nTPM); high antibody staining in 6 normal tissues; highest cancer staining testis cancer (12 of 12 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), Testicular germ cell tumours, Lymphoma); approvals of single-target medicines aimed at it also list Sarcomas (soft tissue, bone, GIST), Neuroendocrine tumours, Childhood cancers (all types), Gestational trophoblastic neoplasia and more, not counted; Open Targets associates it with 15 specific cancer types at or above 0.5 (breast cancer, acute myeloid leukemia, plasma cell myeloma, small cell lung carcinoma, Kaposi's sarcoma, Hodgkins lymphoma and more). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas TOP2A tissue","url":"https://www.proteinatlas.org/ENSG00000131747-TOP2A/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000131747 associations","url":"https://platform.opentargets.org/target/ENSG00000131747/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11989","ensembl":"ENSG00000131747","uniprot":"P11388","entrez":"7153","firstDescribed":1988,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Tsai-Pflugfelder et al, Proc. Natl. Acad. Sci. U.S.A, 1988, \"Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2845399/","biology":"Type IIA topoisomerase, proliferation-associated isoform; poisoned by etoposide and anthracyclines into a stable cleavage complex.","whereFound":["Proliferating tumour cells; TOP2A amplification in a subset of HER2-positive breast cancers"],"targetClass":"enzyme","prevalence":[{"cancerId":"breast-her2-positive","pct":"about 35","measure":"TOP2A co-amplification with HER2, FISH, 4,943 breast cancers analysed","source":"https://doi.org/10.1200/JCO.2009.27.5644","note":"Co-amplified tumours gained most from anthracycline-containing chemotherapy"}]},"route":"/targets/top2a/","neighbours":{"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"},{"id":"testicular","kind":"cancer","name":"Testicular germ cell tumours","route":"/cancers/testicular/"}],"drug":[{"id":"aldoxorubicin","kind":"drug","name":"Aldoxorubicin","route":"/drugs/aldoxorubicin/"},{"id":"amrubicin","kind":"drug","name":"Amrubicin","route":"/drugs/amrubicin/"},{"id":"amsacrine","kind":"drug","name":"Amsacrine","route":"/drugs/amsacrine/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"pirarubicin","kind":"drug","name":"Pirarubicin","route":"/drugs/pirarubicin/"},{"id":"pixantrone","kind":"drug","name":"Pixantrone","route":"/drugs/pixantrone/"},{"id":"teniposide","kind":"drug","name":"Teniposide","route":"/drugs/teniposide/"}]}}