ArticleCancer research2022
Repurposing Ceritinib Induces DNA Damage and Enhances PARP Inhibitor Responses in High-Grade Serous Ovarian Carcinoma.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- XYL-1 and Olaparib Synergistically Inhibit the Growth of Pancreatic Cancer by Suppressing the SCD1/BRCA1 Signaling Pathway.Molecules (Basel, Switzerland) · 2026Article
- Dual FAK and EPHA2 targeting by brigatinib tackles PARP inhibitor adaptive survival response in high-grade serous ovarian cancer.Science translational medicine · 2026Article
- Mechanistic models position ceritinib as a nuclear integrity disrupting therapy in pediatric liver tumors.Journal of experimental & clinical cancer research : CR · 2025Article
- Dual-responsive nanoscale ultrasound contrast agent as an oxidative stress amplifier for enhanced DNA damage in BRCA-proficient ovarian cancer.Materials today. Bio · 2025Article
- Antitumor activity of rucaparib plus PLX038A in serous endometrial carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Exploring Strategies to Prevent and Treat Ovarian Cancer in Terms of Oxidative Stress and Antioxidants.Antioxidants (Basel, Switzerland) · 2025Review
- Crizotinib Enhances PARP Inhibitor Efficacy in Ovarian Cancer Cells and Xenograft Models by Inducing Autophagy.Molecular cancer research : MCR · 2024Article
- Mechanism of PARP inhibitor resistance and potential overcoming strategies.Genes & diseases · 2024Review
- Therapeutic Targeting of DNA Damage Repair in the Era of Precision Oncology and Immune Checkpoint Inhibitors.Journal of immunotherapy and precision oncology · 2023Review
- Kinase Inhibitors in the Treatment of Ovarian Cancer: Current State and Future Promises.Cancers · 2022Review
- Effects of cancer-associated point mutations on the structure, function, and stability of isocitrate dehydrogenase 2.Scientific reports · 2022Article
- Olaparib synergizes with arsenic trioxide by promoting apoptosis and ferroptosis in platinum-resistant ovarian cancer.Cell death & disease · 2022Article
- PARP inhibitor resistance in breast and gynecological cancer: Resistance mechanisms and combination therapy strategies.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
PARP inhibitors (PARPi) have activity in homologous recombination (HR) repair-deficient, high-grade serous ovarian cancers (HGSOC). However, even responsive tumors develop PARPi resistance, highlighting the need to delay or prevent the appearance of PARPi resistance. Here, we showed that the ALK kinase inhibitor ceritinib synergizes with PARPis by inhibiting complex I of the mitochondrial electron transport chain, which increases production of reactive oxygen species (ROS) and subsequent induction of oxidative DNA damage that is repaired in a PARP-dependent manner. In addition, combined treatment with ceritinib and PARPi synergized in HGSOC cell lines irrespective of HR status, and a combination of ceritinib with the PARPi olaparib induced tumor regression more effectively than olaparib alone in HGSOC patient-derived xenograft (PDX) models. Notably, the ceritinib and olaparib combination was most effective in PDX models with preexisting PARPi sensitivity and was well tolerated. These findings unveil suppression of mitochondrial respiration, accumulation of ROS, and subsequent induction of DNA damage as novel effects of ceritinib. They also suggest that the ceritinib and PARPi combination warrants further investigation as a means to enhance PARPi activity in HGSOC, particularly in tumors with preexisting HR defects. SIGNIFICANCE: The kinase inhibitor ceritinib synergizes with PARPi to induce tumor regression in ovarian cancer models, suggesting that ceritinib combined with PARPi may be an effective strategy for treating ovarian cancer.
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