ArticleFrontiers in oncology2023
PARP inhibitors in the treatment of ARID1A mutant ovarian clear cell cancer: PI3K/Akt1-dependent mechanism of synthetic lethality.
Article in Frontiers in oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- PARP Inhibitors as Radiosensitizers: Current Evidence and Future Directions.Current oncology reports · 2026Review
- Co-targeting cystathionine gamma-lyase and mTOR: a promising therapeutic strategy in clear cell ovarian cancer.BMC cancer · 2026Article
- BMAL2 is a druggable target for ovarian clear cell carcinoma (OCCC).EMBO molecular medicine · 2026Article
- Liposomal Vitamin C as a Modulator of the Efficacy of Ceralasertib Therapy in Ovarian Cancer.International journal of molecular sciences · 2026Article
- Molecular profile and targeted therapies for ovarian clear cell ovarian cancer.Therapeutic advances in medical oncology · 2026Review
- Enhancing PARP inhibitor efficacy in ovarian cancer: targeting the PI3K/AKT/mTOR pathway.Journal of ovarian research · 2025Review
- Establishment of novel cholangiocarcinoma cell lines with ARID1A deficiency and preclinical validation of synthetic lethality therapies.Scientific reports · 2025Article
- Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolution.Communications biology · 2025Article
- Ovarian clear cell carcinoma: open questions on the management and treatment algorithm.The oncologist · 2025Review
- Potentially actionable molecular alterations in particular related to poor oncologic outcomes in salivary gland carcinomas.BMC cancer · 2025Article
- DNA damage response inhibitors in cancer therapy: lessons from the past, current status and future implications.Nature reviews. Drug discovery · 2025Review
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
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Authors and funding
4 authors.
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Abstract
Introduction: Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme involved in the repair of DNA single-strand breaks (SSB). The recent development of poly(ADP-ribose) polymerase inhibitors (PARPi) results from over 45 years of studies. When the activity of PARP1 or PARP2 is compromised, DNA SSB lesions are unresolved and can be converted to DNA double-strand breaks (DSBs) by the cellular transcription mechanisms. ARID1A (also called BAF250a) is an important component of the mammalian Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex. ARID1A gene demonstrates >50% of mutation rate in ovarian clear-cell carcinomas (OCCC). Mutated or downregulated ARID1A significantly compromises the Homologous Recombination Repair (HRR) of DNA DSB. Results: The present study demonstrated that downregulated or mutated ARID1A attenuates DNA HRR through stimulation of the PI3K/Akt1 pathway and makes tumor cells highly sensitive to PARPi and PARPi/ionizing radiation (IR) combination. We showed that PI3K/Akt1 pathway plays an important role in the sensitization of cancer cell lines with compromised function of ARID1A to PARPi treatment. Discussion: We believe that using of PARPi monotherapy or in combination with radiation therapy is an appealing strategy for treating ARID1A-mutated cancers, as well as many other types of PI3K/Akt1-driven cancers.
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