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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.
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.
In plain words · 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.
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.
Type IIA topoisomerase, proliferation-associated isoform; poisoned by etoposide and anthracyclines into a stable cleavage complex.
6 products aim at Topoisomerase II alpha (TOP2A): small molecules and other agents. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
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.)
Sources: Human Protein Atlas TOP2A tissue; Open Targets ENSG00000131747 associations
First described 1988. 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". Source.
Type IIA topoisomerase, proliferation-associated isoform; poisoned by etoposide and anthracyclines into a stable cleavage complex.
RNA: tissue enhanced (lymphoid tissue 119 nTPM, testis 62 nTPM), detected in many normal tissues.
Medium: Appendix, Cervix, Colon, Duodenum, Endometrium, Esophagus, Oral mucosa, Prostate.
Medium only: prostate cancer, thyroid cancer.
HPA TOP2A tissue · HPA TOP2A pathology · HPA protein class: Essential proteins, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| HER2-positive breast cancer | about 35% | TOP2A co-amplification with HER2, FISH, 4,943 breast cancers analysed | Co-amplified tumours gained most from anthracycline-containing chemotherapy | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Aldoxorubicin is doxorubicin, the workhorse chemotherapy nicknamed the red devil, attached to a linker that hitches it to the body's own albumin so more reaches the tumour and less reaches the heart; it beat doxorubicin in a randomised phase 2 sarcoma trial but missed the primary endpoint of its phase 3, and a new company is now trying to finish its development.
Amrubicin is a Japanese anthracycline approved there in 2002 for small cell and non-small cell lung cancer, a standard second-line option for small cell lung cancer in Japan that failed to beat topotecan in a Western phase 3 trial and now serves as the comparator in global trials.
Amsacrine is an intravenous leukaemia drug, approved in Europe, Canada and Australia in the 1980s, used mainly for acute myeloid leukaemia that has relapsed or resisted anthracycline-based treatment.
Pirarubicin is a doxorubicin relative developed in Japan and used there and in China for breast cancer, lymphoma, bladder cancer and other tumours, including instillation into the bladder after tumour resection.
Pixantrone is an anthracycline-like drug engineered to spare the heart. The European Union authorised it in 2012 as a single agent for adults with aggressive B-cell lymphoma that had relapsed several times; the authorisation expired in June 2024 when the company did not renew it.
Teniposide is a close relative of etoposide approved in the United States in 1992 for children whose acute lymphoblastic leukaemia has come back after induction, and used in Europe for childhood brain tumours and neuroblastoma.
Query for this target: (TITLE:"Topoisomerase II alpha" OR ABSTRACT:"Topoisomerase II alpha" OR TITLE:"TOP2A" OR ABSTRACT:"TOP2A") 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 Topoisomerase II alpha (TOP2A), not a curated reading list.
Shares Teniposide, Etoposide, Small-cell lung cancer.
Shares Pixantrone, Etoposide.
Shares Testicular germ cell tumours, Etoposide, Doxorubicin, Small-cell lung cancer.
Shares Amrubicin, Small-cell lung cancer.
Shares Amrubicin, Small-cell lung cancer.