ArticleOncogene2021
Molecular disruption of DNA polymerase β for platinum sensitisation and synthetic lethality in epithelial ovarian cancers.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial.Nature communications · 2024Trial
- Oocyte-specific knockout of eIF2B subunits causes apoptosis of mouse oocytes within the early growing follicles via DNA damage and mitochondrial dysfunction.Cell death & disease · 2026Article
- Anticancer sensitivities and biological characteristics of HCT116 cells resistant to the selective poly(ADP-ribose) glycohydrolase inhibitor.FEBS open bio · 2026Article
- Article
- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- Noncompetitive Inhibition of DNA Polymerase β by a Nonnative Nucleotide.The Journal of organic chemistry · 2025Review
- Transcription Factor p73 Is a Predictor of Platinum Resistance and Promotes Aggressive Epithelial Ovarian Cancers.International journal of molecular sciences · 2025Article
- Harnessing DNA polymerase beta defect enhances synthetic lethality and treatment response in gastric cancer cells: implication for immunotherapy.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2025Review
- Article
- Article
- Molecular editing ofRSC medicinal chemistry · 2024Article
- Siglec-7 glyco-immune binding mAbs or NK cell engager biologics induce potent antitumor immunity against ovarian cancers.Science advances · 2023Article
- Anti-cancer activity of ultra-short single-stranded polydeoxyribonucleotides.Investigational new drugs · 2023Article
- Evolving DNA repair synthetic lethality targets in cancer.Bioscience reports · 2022Article
- Targeting Mre11 overcomes platinum resistance and induces synthetic lethality in XRCC1 deficient epithelial ovarian cancers.NPJ precision oncology · 2022Article
- Can Cisplatin Therapy Be Improved? Pathways That Can Be Targeted.International journal of molecular sciences · 2022Review
- Suppression of DNA Polymerase β Activity Is Synthetically Lethal in BRCA1-Deficient Cells.ACS chemical biology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting PARP1 [Poly(ADP-Ribose) Polymerase 1] for synthetic lethality is a new strategy for BRCA germ-line mutated or platinum sensitive ovarian cancers. However, not all patients respond due to intrinsic or acquired resistance to PARP1 inhibitor. Development of alternative synthetic lethality approaches is a high priority. DNA polymerase β (Polβ), a critical player in base excision repair (BER), interacts with PARP1 during DNA repair. Here we show that polβ deficiency is a predictor of platinum sensitivity in human ovarian tumours. Polβ depletion not only increased platinum sensitivity but also reduced invasion, migration and impaired EMT (epithelial to mesenchymal transition) of ovarian cancer cells. Polβ small molecular inhibitors (Pamoic acid and NSC666719) were selectively toxic to BRCA2 deficient cells and associated with double-strand breaks (DSB) accumulation, cell cycle arrest and increased apoptosis. Interestingly, PARG [Poly(ADP-Ribose) Glycohydrolase] inhibitor (PDD00017273) [but not PARP1 inhibitor (Olaparib)] was synthetically lethal in polβ deficient cells. Selective toxicity to PDD00017273 was associated with poly (ADP-ribose) accumulation, reduced nicotinamide adenine dinucleotide (NAD
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