ArticleNature communications2024
Discovery of a small-molecule inhibitor that traps Polθ on DNA and synergizes with PARP inhibitors.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25citing papers in PubMed
9.8field-weighted citation impact, top 1% of its field
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- DNA polymerase theta (Polθ): a novel candidate for targeted cancer therapy.Cancer biology & therapy · 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
- Targeting Polθ Helicase with RP-3467: Preclinical Validation and Clinical Response in a gmedRxiv : the preprint server for health sciences · 2026Article
- Activation of Pol theta-mediated end joining begins during mitotic commitment.bioRxiv : the preprint server for biology · 2026Article
- Preoperative PARP Inhibitors in Ovarian Cancer Trials: Connecting Molecular Oncology and Cytoreductive Surgery.Cancers · 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
- Structures of human telomerase with BIBR1532 reveal novel mechanism of inhibition.Nature chemical biology · 2026Article
- Review
- Polθ activity modulates sensitivity to standard therapies in DNMT3A-deficient leukemia.Cell reports. Medicine · 2026Article
- Interplay between autophagy and p38 MAPK during salinomycin-induced cell death in cisplatin-resistant melanoma.Scientific reports · 2026Article
- Removing therapy-induced senescent cancer cells targets and potentiates the response of pancreatic cancer cells toward PARP inhibitors as maintenance therapy.Apoptosis : an international journal on programmed cell death · 2026Article
- A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy.Oncology research · 2026Review
- EP300 deficiency leads to chronic replication stress mediated by defective replication fork protection.Nature communications · 2025Article
- Emerging insights into alternative end‑joining: Mechanisms, genome instability and therapeutic opportunities in cancer (Review).International journal of oncology · 2025Review
- RTx-303, an Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates PARP Inhibitors in BRCA Mutant Tumors.Journal of medicinal chemistry · 2025Article
- Dual-Target Therapeutic Strategies in Triple-Negative Breast Cancer: Mechanistic Insights and Clinical Potential.Cancers · 2025Review
- Epigenetic synthetic lethality as a cancer therapeutic strategy: synergy of experimental and computational approaches.Epigenomics · 2025Review
- Targeting RAD52 overcomes PARP inhibitor resistance in preclinicalbioRxiv : the preprint server for biology · 2025Article
- Review
- Division of labor within polymerase theta in repair of CRISPR-induced DNA breaks inPNAS nexus · 2025Article
Corrections and comments
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Authors and funding
23 authors at 7 institutions in 1 country.
William Fried *Molecular and Computational Biology, Department of Biological Sciences and Chemistry, University of Southern California, Los Angeles, CA, USA.
Mrityunjay Tyagi *Department of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Leonid MinakhinDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Gurushankar ChandramoulyDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Taylor TredinnickDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.ORCID http://orcid.org/0000-0002-0106-5194
Mercy RamanjuluRecombination Therapeutics, Pennsylvania Biotechnology Center, Doylestown, PA, 18902, USA.
William AuerbacherDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Marissa CalbertDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.ORCID http://orcid.org/0000-0003-3005-8679
Timur RusanovDepartment of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA.
Trung HoangJanssen Biotech, Malvern, PA, 19355, USA.
Nikita BorisonnikPolysciences, Inc., Huntingdon Valley, PA, USA.
Robert BetschNuclear Dynamics Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
John J KraisNuclear Dynamics Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.ORCID http://orcid.org/0000-0002-3916-3435
Yifan WangNuclear Dynamics Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
Umeshkumar M VekariyaFels Cancer Institute for Personalized Medicine, Philadelphia, PA, USA.
John GordonFels Cancer Institute for Personalized Medicine, Philadelphia, PA, USA.
George MortonMoulder Center for Drug Discovery Research, Temple University School of Pharmacy, Philadelphia, PA, USA.
Tatiana KentDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Tomasz SkorskiFels Cancer Institute for Personalized Medicine, Philadelphia, PA, USA.
Neil JohnsonNuclear Dynamics Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.ORCID http://orcid.org/0000-0002-0276-0009
Wayne ChildersRecombination Therapeutics, Pennsylvania Biotechnology Center, Doylestown, PA, 18902, USA.
Xiaojiang S ChenMolecular and Computational Biology, Department of Biological Sciences and Chemistry, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-9574-0551
Richard T PomerantzDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA. richard.pomerantz@jefferson.edu.ORCID http://orcid.org/0000-0003-1194-9871
Thomas Jefferson University · USFox Chase Cancer Center · USTemple University · USUniversity of Southern California · USJanssen (United States) · USPolysciences (United States) · USUniversity of Illinois Chicago · US
Funding
Targeting DNA repair to eradicate TKi-refractory/resistant CML and Ph+ALLR01CA186238 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI SKORSKI, TOMASZ · 2014 to 2024
$4.5MCompensatory Mechanisms that Promote Homologous Recombination in BRCA1 Mutant CancersR01CA214799 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Neil Johnson · 2017 to 2026
$4.3MPolQ as a novel therapeutic target in AMLR01CA244179 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI POMERANTZ, RICHARD T, SKORSKI, TOMASZ · 2020 to 2024
$2.7MAssessing DNA Polymerase Theta as a Therapeutic Target in BRCA1 Mutant CancerR01CA262466 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Neil Johnson · 2022 to 2026
$2.3MNovel Mechanisms and Regulation of Mammalian Double-Strand Break RepairR35GM152198 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI Richard T Pomerantz · 2024 to 2026
$2.1MDissecting BRCA1-PALB2 Activity in DNA Repair and DevelopmentR01GM135293 · NIGMS · RESEARCH INST OF FOX CHASE CAN CTR · PI JOHNSON, NEIL · 2020 to 2023
$1.9MStructure and Function of DNA Polymerase ThetaR01GM130889 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI POMERANTZ, RICHARD T · 2019 to 2022
$1.6MMechanisms of RNA-DNA repairR01GM137124 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI POMERANTZ, RICHARD T · 2020 to 2023
$1.5MNCI NIH HHS R01 CA186238NCI NIH HHS R01 CA214799NCI NIH HHS R01 CA244179NCI NIH HHS R01 CA262466NIGMS NIH HHS R01 GM130889NIGMS NIH HHS R01 GM135293NIGMS NIH HHS R01 GM137124NIGMS NIH HHS R35 GM152198
Abstract
The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC
Indexed as
BRCA1 ProteinPoly(ADP-ribose) Polymerase InhibitorsBRCA2 ProteinDNADNA-Directed DNA PolymeraseDNA RepairHomologous RecombinationHumansBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanDNADNA-Directed DNA PolymerasePoly(ADP-ribose) Polymerase Inhibitors
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