TOP2A DNA topoisomerase II alpha
ENSG00000131747 · protein coding · Open Targets profile
Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (PubMed:17567603, PubMed:18790802, PubMed:22013166, PubMed:22323612, PubMed:27754753). May play a role in regulating the period length of BMAL1 transcriptional oscillation (By similarity). {ECO:0000250|UniProtKB:Q01320, ECO:0000269|PubMed:17567603, ECO:0000269|PubMed:18790802, ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22323612, ECO:0000269|PubMed:27754753}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- Advanced Clinical
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.36327001452445984 (upper bound 0.4445199966430664). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against TOP2A (dexrazoxane, pazufloxacin, teniposide, mitoxantrone, valrubicin, vosaroxin, idarubicin, daunorubicin, amrubicin, amsacrine, doxorubicin, etoposide), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Alex F HerreraCity of Hope Medical Center · 5 of 5 trials Phase 2+
- Aditi BagchiSt. Jude Children's Research Hospital · 2 of 2 trials Phase 2+
- Amar GajjarSt. Jude Children's Research Hospital · 2 of 2 trials Phase 2+
- Farhad Ravandi-KashaniSWOG Cancer Research Network · 2 of 2 trials Phase 2+
- Franco LocatelliIRCSS Ospedale Pediatrico Bambino Gesù · 2 of 2 trials Phase 2+
- Haidy Mahmoud SamiDelta University · 2 of 2 trials Phase 2+
- Ibrahim AldossCity of Hope Medical Center · 2 of 2 trials Phase 2+
- Jung-min LeeNRG Oncology · 2 of 2 trials Phase 2+
- Luhua (Michael) WangM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Mohamed Abdelhamid AlmeldeinTanta University · 2 of 2 trials Phase 2+
- Robert YarchoanNational Cancer Institute (NCI) · 2 of 2 trials Phase 2+
- Ryan LynchFred Hutch/University of Washington Cancer Consortium · 2 of 2 trials Phase 2+
- Ariela NoyMemorial Sloan Kettering Cancer Center · 1 of 2 trials Phase 2+
- Qingqing CaiSun Yat-Sen University Cancer Center · 1 of 2 trials Phase 2+
- Rahul LakhotiaNational Cancer Institute (NCI) · 1 of 2 trials Phase 2+
Registry trials of dexrazoxane, pazufloxacin, teniposide, mitoxantrone, valrubicin, vosaroxin, idarubicin, daunorubicin, amrubicin, amsacrine, doxorubicin, etoposide updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 245 of 383 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 17 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
728 trials of drugs against TOP2A were stopped early; 3 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of dexrazoxane, pazufloxacin, teniposide, mitoxantrone, valrubicin, vosaroxin, idarubicin, daunorubicin, amrubicin, amsacrine, doxorubicin, etoposide, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 728.
- terminated · 2026-11-04 · City of Hope Medical Center · etoposide phosphate“Terminated early due a shift in resources after lackluster performance of the drug.”
- terminated · 2026-10-28 · Bristol-Myers Squibb · Pegylated Liposomal Doxorubicin (PLD)“Business objectives have changed.”
- suspended · 2026-10-27 · National Cancer Institute (NCI) · Doxorubicin Hydrochloride“Other - Extend the observation period for current patients”
- withdrawn · 2026-10-22 · City of Hope Medical Center · Pegylated Liposomal Doxorubicin Hydrochloride“Budgetary constraints”
- terminated · 2026-10-21 · Medical College of Wisconsin · Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen“No longer have funding support to complete the pharmacogenetics component.”
- terminated · 2026-10-19 · Novartis Pharmaceuticals · Pegylated liposomal doxorubicin (PLD)“Sponsor Decision”
- terminated · 2026-10-06 · Alaunos Therapeutics · doxorubicin“Primary endpoint (PFS) not met at the final analysis; sponsor decided to stop the study before the planned final overall survival analysis.”
- terminated · 2026-10-05 · Alaunos Therapeutics · Doxorubicin“Sponsor stopped enrollment at 67 of about 100 planned participants after an unplanned interim analysis confirmed the primary PFS endpoint had been reached. Enrolled participants were followed to their PFS endpoint.”
- terminated · 2026-10-05 · Children's Oncology Group · Doxorubicin Hydrochloride, Etoposide“Drug supply issues”
- terminated · 2026-10-01 · Alaunos Therapeutics · Etoposide“Sponsor closed enrollment in April 2013 following a change in the palifosfamide development plan (business decision), not for safety reasons. Enrolled participants continued treatment and were followed for survival”
- suspended · 2026-09-29 · University of Washington · Doxorubicin, Etoposide“Safety Review”
- withdrawn · 2026-09-23 · M.D. Anderson Cancer Center · Daunorubicin“PI requested”
- terminated · 2026-09-18 · Pusan National University Yangsan Hospital · matched by the registry's drug synonyms“Poor accrual due to increased use of alternative neoadjuvant treatment options.”
- suspended · 2026-09-14 · University of Maryland, Baltimore · Etoposide Injection“PI changed institution. Not yet approved at current location.”
- suspended · 2026-09-01 · CStone Pharmaceuticals · Doxorubicin“The sponsor is temporarily pausing the trial to evaluate existing clinical data for long-term benefit-risk and optimize doses and dosing schedule.”
- terminated · 2026-08-18 · T-ACE Medical Co., Ltd · matched by the registry's drug synonyms“T-ACE Medical Co., Ltd. hereby submits this formal notification to the U.S. Food and Drug Administration (FDA) to request the permanent discontinuation and withdrawal of Investigational New Drug application IND 152626.”
- terminated · 2026-07-30 · M.D. Anderson Cancer Center · Doxorubicin Hydrochloride“the study was closed early due to competing trials”
- terminated · 2026-07-27 · M.D. Anderson Cancer Center · Pegylated Liposomal Doxorubicin Hydrochloride“<75% participation”
- withdrawn · 2026-07-16 · Tianjin Medical University Cancer Institute and Hospital · matched by the registry's drug synonyms“Following an evaluation by the investigator, the study has been terminated due to exceptional circumstances.”
- terminated · 2026-06-01 · Northwestern University · Idarubicin“Low accrual”
- withdrawn · 2026-05-14 · Institute of Hematology & Blood Diseases Hospital, China · matched by the registry's drug synonyms“drug-associated adverse reactions”
- suspended · 2026-05-13 · National Cancer Centre, Singapore · matched by the registry's drug synonyms“Awaiting further funding.”
- terminated · 2026-05-04 · Debiopharm International SA · Etoposide“The trial was concluded for strategic reasons.”
- withdrawn · 2026-04-29 · Sichuan University · Etoposide“Inorder to avoid the serious adverse effect of Toripalimab combining with Tifcemalimab, considering as the protection of participants.”
- terminated · 2026-04-28 · Chia Tai Tianqing Pharmaceutical Group Co., Ltd. · Carboplatin for injection/cisplatin for injection + etoposide injection + benmelstobart injection + Anlotinib hydrochloride capsule, Carboplatin for injection/Cisplatin for injection + etoposide injection + Tislelizumab injection“This study was closed due to business reasons. Closure was not prompted by any safety or efficacy concerns.”
Paediatric incentives and obligations for TOP2A's drugs
For dexrazoxane, pazufloxacin, teniposide, mitoxantrone, valrubicin, vosaroxin, idarubicin, daunorubicin, amrubicin, amsacrine, doxorubicin, etoposide: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · TOP2A is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-001858-PIP02-16-M04 (daunorubicin;cytarabine, Treatment of acute myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 25 Oct 2024; EMEA-002043-PIP01-16 (doxorubicin hydrochloride, Treatment of hepatocellular carcinoma): W: decision granting a waiver in all age groups for all conditions or indications, 31 Jan 2017; EMEA-001450-PIP01-13-M01 (vosaroxin, Treatment of acute myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 4 Dec 2015Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/25/3056 positive 22 May 2025: Treatment of soft-tissue sarcoma; EU/3/22/2624 positive 21 Jun 2022: Treatment of soft tissue sarcoma; EU/3/10/833 positive 23 Feb 2011: Treatment of hepatocellular carcinoma; EU/3/12/1006 withdrawn 28 Nov 2012: Treatment of glioma; +8 moreRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Zolsketil pegylated liposomal: authorised since 31 May 2022; Vyxeos liposomal (previously Vyxeos): authorised since 23 Aug 2018, orphan medicine; Caelyx pegylated liposomal: authorised since 20 Jun 1996; Celdoxome pegylated liposomal: lapsed since 15 Sept 2022; +6 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: yes · Daunorubicin and cytarabine liposome [Vyxeos], 30 Mar 2021: Treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older; Daunorubicin Hydrochloride, 19 Dec 1979: In combination with other approved anticancer drugs, for remission induction in acute lymphocytic leukemia of children and adults; Doxorubicin Hydrochloride, 7 Aug 1974: MULTIPLERule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 1220 interventional studies of dexrazoxane, pazufloxacin, teniposide, mitoxantrone, valrubicin, vosaroxin, idarubicin, daunorubicin, amrubicin, amsacrine, doxorubicin, etoposide include patients under 18; 234 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 24 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.