POLD1 DNA polymerase delta 1, catalytic subunit
ENSG00000062822 · protein coding · Open Targets profile
As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24022480, PubMed:24035200, PubMed:31449058). Exhibits both DNA polymerase and 3'- to 5'- exonuclease activities (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24022480, PubMed:24035200). Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol- delta3 compared with that of Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine, 8oxoG or abasic sites (PubMed:19074196, PubMed:24191025). {ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24022480, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24191025, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:31449058}.
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 Withdrawn means the drug was pulled from the market or from development.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, Druggable Family
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.6090800166130066 (upper bound 0.7344300150871277). 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 POLD1 (gemcitabine, fludarabine, troxacitabine, aspacytarabine), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Christopher G KanakryNational Cancer Institute (NCI) · 3 of 4 trials Phase 2+Ph1/Ph2NCT05436418 · The Lowest Effective Dose of Post-Transplantation Cyclophosphamide in Combination With Sirolimus and Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis After Reduced Intensity Conditioning and Peripheral Blood Stem Cell Transplantationbrief
- James C YangNational Cancer Institute (NCI) · 3 of 3 trials Phase 2+Ph1/Ph2NCT03190941 · Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patientsbrief
- Christian S HinrichsRutgers Cancer Institute · 2 of 3 trials Phase 2+
- Steven A RosenbergNational Cancer Institute (NCI) · 2 of 3 trials Phase 2+
- Yihong YaoAbelZeta Inc. · 2 of 3 trials Phase 2+Ph2NCT07875413 · Prizloncabtagene Autoleucel (Prizlon-cel) for the Treatment of Relapsed or Refractory Large B-cell Lymphoma Post FDA Approved CAR T-cell Therapybrief
- Alison MoskowitzMemorial Sloan Kettering Cancer Center · 2 of 2 trials Phase 2+
- Monzr M Al MalkiCity of Hope Medical Center · 2 of 2 trials Phase 2+Ph2NCT04262843 · Total Marrow and Lymphoid Irradiation as Conditioning Regimen Before Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome or Acute LeukemiabriefPh2NCT07582172 · Total Marrow and Lymphoid Irradiation in Combination With Fludarabine and Melphalan as Conditioning for Allogeneic Peripheral Blood Stem Cell Hematopoietic Cell Transplant in Older Patients With Refractory and Relapsed Acute Myeloid Leukemia and High-risk Myelodysplastic Syndromebrief
- Sara K SilbertNational Cancer Institute (NCI) · 2 of 2 trials Phase 2+
- Uday R PopatM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- James N KochenderferNational Cancer Institute (NCI) · 1 of 3 trials Phase 2+
- Rodabe N AmariaM.D. Anderson Cancer Center · 1 of 3 trials Phase 2+Ph1/Ph2NCT06598371 · A Phase 1/2 Study of KSQ-004EX, Autologous Tumor Infiltrating Lymphocytes Engineered to Inactivate Genes Encoding SOCS1 and Regnase-1, in Patients With Select Advanced Solid Tumorsbrief
- Matthew FrigaultMassachusetts General Hospital · 1 of 2 trials Phase 2+
- Qiang LiuTianjin Medical University General Hospital · 1 of 2 trials Phase 2+
- Seth KarolSt. Jude Children's Research Hospital · 1 of 2 trials Phase 2+
- A P ChenNational Cancer Institute LAO · 1 of 1 trials Phase 2+
Registry trials of gemcitabine, fludarabine, troxacitabine, aspacytarabine 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; 282 of 386 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. 14 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
1086 trials of drugs against POLD1 were stopped early; 6 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of gemcitabine, fludarabine, troxacitabine, aspacytarabine, 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 1086.
- suspended · 2026-11-10 · National Cancer Institute (NCI) · gemcitabine“Placed on voluntary hold to new recruitment pending modification to combination monoclonal antibody treatment.”
- suspended · 2026-11-04 · Masonic Cancer Center, University of Minnesota · Fludarabine“Accrual met”
- suspended · 2026-11-04 · Institute of Hematology & Blood Diseases Hospital, China · matched by the registry's drug synonyms“Suboptimal treatment response”
- terminated · 2026-11-04 · InnoPharmax Inc. · matched by the registry's drug synonyms“Dose-finding stage has been completed, and dose-expanding stage was not conducted due to design amendment.”
- terminated · 2026-11-03 · Columbia University · Gemcitabine“Change in standard of care treatment for muscle-invasive bladder cancer”
- suspended · 2026-11-03 · National Cancer Institute (NCI) · Gemcitabine Hydrochloride“Drug Supply Issues”
- terminated · 2026-10-30 · Shenzhen Geno-Immune Medical Institute · matched by the registry's drug synonymsNo reason given
- terminated · 2026-10-29 · Arsenal Biosciences, Inc. · matched by the registry's drug synonyms“Active patients have been rolled over to a separate LTFU study.”
- terminated · 2026-10-29 · Hebei Yanda Ludaopei Hospital · matched by the registry's drug synonyms“Sponsor decision to discontinue the study; the study is no longer being pursued due to sponsor strategic reprioritization and resource allocation. The decision was not based on safety concerns. Enrolled participants will complete safety follow-up per”
- terminated · 2026-10-27 · Adicet Therapeutics · Fludarabine“Sponsor decision”
- terminated · 2026-10-27 · Brandon Huffman, MD · matched by the registry's drug synonyms“Study stopped early due to reaching the minimum number of DLTs required for halting the study due to toxicity.”
- terminated · 2026-10-19 · Boston Children's Hospital · Fludarabine“Funding terminated”
- suspended · 2026-10-16 · National Cancer Institute (NCI) · Fludarabine“Placed on hold to conduct a review of events on study.”
- suspended · 2026-10-15 · City of Hope Medical Center · Fludarabine“Timeline Adjustment”
- withdrawn · 2026-10-15 · Beijing Boren Hospital · matched by the registry's drug synonyms“No participants.”
- suspended · 2026-09-28 · City of Hope Medical Center · Fludarabine“Accrual goal”
- terminated · 2026-09-25 · Takeda · matched by the registry's drug synonyms“Sponsor decision (No safety concern)”
- withdrawn · 2026-09-24 · Case Comprehensive Cancer Center · matched by the registry's drug synonyms“PI left institution”
- terminated · 2026-09-17 · Centre Oscar Lambret · Gemcitabine“Problems of recruitment”
- suspended · 2026-09-15 · Roswell Park Cancer Institute · Fludarabine“awaiting agreement with Sponsor”
- terminated · 2026-09-14 · Merck Sharp & Dohme LLC · Gemcitabine“Business Reasons”
- withdrawn · 2026-09-11 · Fred Hutchinson Cancer Center · Fludarabine Phosphate“Study withdrawn before opening to accrual.”
- suspended · 2026-09-11 · Chongqing Precision Biotech Co., Ltd · matched by the registry's drug synonyms“Sponsor stopped the study.”
- suspended · 2026-09-10 · Leland Metheny · Fludarabine“insufficient funding”
- terminated · 2026-09-08 · ETOP IBCSG Partners Foundation · matched by the registry's drug synonyms“Completion of recruitment was not feasible as accrual was slower than anticipated. Even if a benefit for denosumab could be shown, these results would be of very limited clinical impact by the time they would be available”
Paediatric incentives and obligations for POLD1's drugs
For gemcitabine, fludarabine, troxacitabine, aspacytarabine: 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 · POLD1 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 · EMA/PE/0000230592 (gemcitabine hydrochloride, condition not given): W: decision granting a waiver in all age groups for all conditions or indications, 14 Apr 2025; EMEA-003007-PIP01-21 (gemcitabine hydrochloride, Treatment of urothelial carcinoma): W: decision granting a waiver in all age groups for all conditions or indications, 13 Aug 2021Rule: 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/3/23/2782 positive 22 May 2023: Treatment of myelodysplastic syndromes; EU/3/20/2371 positive 9 Dec 2020: Treatment of acute myeloid leukaemia; EU/3/05/311 withdrawn 26 Aug 2005: Treatment of acute myeloid leukaemiaRule: 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: no · EMA lists no centrally authorised medicine of gemcitabine, fludarabine, troxacitabine, aspacytarabineRule: 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: no · FDA's table lists no pediatric approval of gemcitabine, fludarabine, troxacitabine, aspacytarabineRule: 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 · 1073 interventional studies of gemcitabine, fludarabine, troxacitabine, aspacytarabine include patients under 18; 294 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 7 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.