ArticleCancer chemotherapy and pharmacology2022
An effective AKT inhibitor-PARP inhibitor combination therapy for recurrent ovarian cancer.
Article in Cancer chemotherapy and pharmacology, 2022. 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, 16 citations in OpenAlex.
- PARP-2 catalytic activity drives replication-ICL repair in an allele-specific manner during germline development.PLoS genetics · 2026Article
- Enhancing PARP inhibitor efficacy in ovarian cancer: targeting the PI3K/AKT/mTOR pathway.Journal of ovarian research · 2025Review
- Low Serum Cholinesterase Levels Predict Poor Prognosis in Patients with Ovarian Cancer.International journal of general medicine · 2025Article
- Alkaloid-driven multi-target synergy ofFrontiers in pharmacology · 2025Article
- AKT inhibitors in gynecologic oncology: past, present and future.Frontiers in oncology · 2025Review
- AKT-dependent nuclear localization of EPRS1 activates PARP1 in breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Uncovering miRNA-mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization ofCells · 2024Article
- The combination of breast cancer PDO and mini-PDX platform for drug screening and individualized treatment.Journal of cellular and molecular medicine · 2024Article
- Bidirectional pharmacokinetic drug interactions between olaparib and metformin.Cancer chemotherapy and pharmacology · 2024Article
- Review
- OncoVee™-MiniPDX-guided anticancer treatment for HER2-negative intermediate-advanced gastric cancer patients: a single-arm, open-label phase I clinical study.Discover oncology · 2023Article
- Kinase Inhibitors in the Treatment of Ovarian Cancer: Current State and Future Promises.Cancers · 2022Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough the use of PARP inhibitor has received considerable amount of attention in ovarian cancer, PARP inhibitor resistance still emerges with disease progression. PI3K/AKT pathway inhibitors have been proposed to synergize with PARP inhibition to slow tumor growth, but the exact molecular mechanisms are still elusive.
methodsUtilizing tumor samples from recurrent EOC patients with platinum resistance and prior PARP inhibitor use, Mini PDX and PDX models were established to study the anti-tumor effect of AKT inhibitor (LAE003) and LAE003/PARP inhibitor (Olaparib) in combination. Five ovarian cancer cell lines were treated with Olaparib or LAE003 or in combination in vitro. Cell viability and apoptosis rate were measured after the treatments. Combination index by the Chou-Talalay was used to evaluate in vitro combination effect of Olaparib and LAE003. The protein expression level of PARP1 and PAR was measured by Western blot in cell lines and by immunohistochemistry in PDX tumor tissues.
resultsTumor cells from two out of five platinum-resistant ovarian cancer patients previously treated with PARP inhibitor were sensitive to AKT inhibition in Mini-PDX study. Inhibition of AKT further increased the response of tumor cells to Olaparib in a PDX model derived from a recurrent platinum-resistant ovarian cancer patient. Additive anti-proliferation effect of LAE003 and Olaparib was also observed in three ovarian cancer cell lines with high PARP1 protein level. Interestingly, mechanism study revealed that AKT inhibition decreased PARP enzyme activity as measured by PAR level and/or reduced PARP1 protein level in the tumor cell lines and PDX tumor tissues, which may explain the observed combined anti-tumor effect of LAE003 and Olaparib.
conclusionCollectively, our results suggest that the combination of AKT inhibitor and PARP inhibitor could be a viable approach for clinical testing in recurrent ovarian cancer patients.
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