ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
Blockage of glutaminolysis enhances the sensitivity of ovarian cancer cells to PI3K/mTOR inhibition involvement of STAT3 signaling.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Enhancing PARP inhibitor efficacy in ovarian cancer: targeting the PI3K/AKT/mTOR pathway.Journal of ovarian research · 2025Review
- In Vitro Inhibition ofPathogens (Basel, Switzerland) · 2025Article
- Therapeutic Potential of Glutaminase Inhibition Targeting Metabolic Adaptations in Resistant Melanomas to Targeted Therapy.International journal of molecular sciences · 2025Article
- Exploring Metabolic Approaches for Epithelial Ovarian Cancer Therapy.Journal of cellular physiology · 2025Review
- mTORC2-driven chromatin cGAS mediates chemoresistance through epigenetic reprogramming in colorectal cancer.Nature cell biology · 2024Article
- Alone and together: current approaches to targeting glutaminase enzymes as part of anti-cancer therapies.Future drug discovery · 2023Review
- STAT proteins in cancer: orchestration of metabolism.Nature reviews. Cancer · 2023Review
- Microglia activation in the mPFC mediates anxiety-like behaviors caused by Staphylococcus aureus strain USA300.Brain and behavior · 2022Article
- Metabolic reprogramming of the tumor immune microenvironment in ovarian cancer: A novel orientation for immunotherapy.Frontiers in immunology · 2022Review
- New progress of glutamine metabolism in the occurrence, development, and treatment of ovarian cancer from mechanism to clinic.Frontiers in oncology · 2022Review
- CRISPR Cas9-mediated ablation of pyruvate carboxylase gene in colon cancer cell line HT-29 inhibits growth and migration, induces apoptosis and increases sensitivity to 5-fluorouracil and glutaminase inhibitor.Frontiers in oncology · 2022Article
- Targeting GLS1 to cancer therapy through glutamine metabolism.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Review
- Regulation and metabolic functions of mTORC1 and mTORC2.Physiological reviews · 2021Review
- Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation.Cells · 2021Review
- Everolimus regulates the activity of gemcitabine-resistant pancreatic cancer cells by targeting the Warburg effect via PI3K/AKT/mTOR signaling.Molecular medicine (Cambridge, Mass.) · 2021Article
- The Role of Succinic Acid Metabolism in Ovarian Cancer.Frontiers in oncology · 2021Review
- Targeting Cancer Metabolism and Current Anti-Cancer Drugs.Advances in experimental medicine and biology · 2021Review
- Targeting the Mitochondrial Metabolic Network: A Promising Strategy in Cancer Treatment.International journal of molecular sciences · 2020Review
- Article
- A comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity.Cell death discovery · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PI3K/Akt/mTOR axis in ovarian cancer is frequently activated and implicated in tumorigenesis. Specific targeting of this pathway is therefore an attractive therapeutic approach for ovarian cancer. However, ovarian cancer cells are resistant to PP242, a dual inhibitor of mTORC1 and mTORC2. Interestingly, blockage of GLS1 with a selective inhibitor, CB839, or siRNA dramatically sensitized the PP242-induced cell death, as evident from increased PARP cleavage. The anti-cancer activity of CB-839 and PP242 was abrogated by the addition of the TCA cycle product α-ketoglutarate, indicating the critical function of GLS1 in ovarian cancer cell survival. Finally, glutaminolysis inhibition activated apoptosis and synergistically sensitized ovarian cancer cells to priming with the mTOR inhibitor PP242. GLS1 inhibition significantly reduced phosphorylated STAT3 expression in ovarian cancer cells. These findings show that targeting glutamine addiction via GLS1 inhibition offers a potential novel therapeutic strategy to overcome resistance to PI3K/Akt/mTOR inhibition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.