ArticleNature cancer2021
A first-in-class Polymerase Theta Inhibitor selectively targets Homologous-Recombination-Deficient Tumors.
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Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers.
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238citing papers in PubMed
20.0field-weighted citation impact, top 1% of its field
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Who cites it
238 citing papers in PubMed, 326 citations in OpenAlex.
- A Phase II Trial of Niraparib in Patients with Advanced Pancreatic Cancer Harboring Pathogenic Variants in ATM, BRCA1, BRCA2, PALB2, and CHEK2.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial.Nature communications · 2024Trial
- DNA polymerase theta (Polθ): a novel candidate for targeted cancer therapy.Cancer biology & therapy · 2026Review
- A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.Annals of medicine · 2026Review
- Ataxia-Telangiectasia, DNA Repair Deficits, Immune Dysfunction, and Cancer: A Review of Mechanisms, Clinical Presentations, and Emerging Therapies.Clinical reviews in allergy & immunology · 2026Review
- Expanding the therapeutic scope of PARP inhibitors in breast cancer: current indications and future directions.The Journal of clinical investigation · 2026Review
- The Pharmacologic Profile of ART6043, a First-in-Class Clinical DNA Polymerase Theta Polymerase Domain Inhibitor Potentiating PARP Inhibitor Efficacy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- The dual immune landscape of homologous recombination-deficient tumors: mechanisms and therapeutic implications.Cancer metastasis reviews · 2026Review
- Targeting Polθ Helicase with RP-3467: Preclinical Validation and Clinical Response in a gmedRxiv : the preprint server for health sciences · 2026Article
- PUM3 is an essential suppressor of replication stress in homologous recombination deficient breast cancer.Nature communications · 2026Article
- Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026Review
- Exploiting DNA damage tolerance for precision oncology.Trends in cancer · 2026Review
- PCNA-RECQL5-RPRD1B recruit repair components to stressed replication forks to promote survival of BRCA1-deficient cancer cells.Nucleic acids research · 2026Article
- Disruption of microhomology-mediated end joining in Ewing sarcoma.Molecular cell · 2026Article
- Defective microhomology-mediated end joining inScience advances · 2026Article
- Apoptosis-driven chromosomal rearrangements in cancer: CAD cleavage, nuclear architecture, and microhomology-mediated end joining.Oncogenesis · 2026Review
- Insights from three decades of BRCA1/2 modeling in mice.Nature genetics · 2026Review
- Overcoming Resistance in Triple-Negative Breast Cancer: A Translational Perspective on Next-Generation DNA Damage Response Inhibitors and Synthetic Lethality.Molecules (Basel, Switzerland) · 2026Review
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
178 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Jia ZhouDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2156-0483
Camille GelotInserm U830, PSL Research University, Institut Curie, Paris, France.
Constantia PantelidouDepartment of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2750-9352
Adam LiDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Hatice YücelInserm U830, PSL Research University, Institut Curie, Paris, France.
Rachel E DavisDepartment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA.
Anniina FärkkiläDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3558-6617
Bose KochupurakkalDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Aleem SyedDepartments of Cancer Biology and Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Geoffrey I ShapiroDepartment of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA, USA.
John A TainerDepartments of Cancer Biology and Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Brian S J BlaggDepartment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA.
Raphael CeccaldiInserm U830, PSL Research University, Institut Curie, Paris, France. raphael.ceccaldi@curie.fr.ORCID http://orcid.org/0000-0003-3049-4278
Alan D D'AndreaDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. alan_dandrea@dfci.harvard.edu.ORCID http://orcid.org/0000-0001-6168-6294
Harvard University · USInserm · FRThe University of Texas MD Anderson Cancer Center · USUniversity of Notre Dame · USDana-Farber Cancer Institute · US
Funding
Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI WALTER J. CHAZIN · 2001 to 2026
$89.6MXenograft CoreP01HL048546 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI GROMPE, MARKUS · 1994 to 2020
$36.4MTissue and Pathology CoreP50CA168504 · NCI · DANA-FARBER CANCER INST · PI Nabihah Tayob · 2013 to 2026
$30.1MMesoscale and Nanoscale Technologies Integrated by Structures for DNA Repair Complexes (MANTIS-DRC)R35CA220430 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI John A. Tainer · 2018 to 2026
$7.6MMOLECULAR PATHOGENESIS OF FANCONI ANEMIAR01HL052725 · NHLBI · DANA-FARBER CANCER INSTITUTE · PI ALAN D. D'ANDREA · 1994 to 2026
$5.9MMolecular Pathogenesis of Fanconi AnemiaR37HL052725 · NHLBI · DANA-FARBER CANCER INSTITUTE · PI D'ANDREA, ALAN D. · 2004 to 2013
$3.9MInvestigating DNA repair vulnerabilities in oncometabolite producing cancersF31CA260794 · NCI · YALE UNIVERSITY · PI NORONHA, KATELYN · 2021 to 2023
$122kNCI NIH HHS F31 CA260794NCI NIH HHS P01 CA092584NCI NIH HHS P50 CA168504NCI NIH HHS R35 CA220430NHLBI NIH HHS P01 HL048546NHLBI NIH HHS R01 HL052725NHLBI NIH HHS R37 HL052725
Abstract
DNA polymerase theta (POLθ) is synthetic lethal with Homologous Recombination (HR) deficiency and thus a candidate target for HR-deficient cancers. Through high-throughput small molecule screens we identified the antibiotic Novobiocin (NVB) as a specific POLθ inhibitor that selectively kills HR-deficient tumor cells
Indexed as
Homologous RecombinationOvarian NeoplasmsAdenosine TriphosphatasesFemaleHumansPoly(ADP-ribose) Polymerase InhibitorsAdenosine TriphosphatasesPoly(ADP-ribose) Polymerase InhibitorsFanconi AnemiaHomologous RecombinationHRD cancerMMEJNovobiocinPARP inhibitor resistancePolymerase theta (POLθ)
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.