ArticleCancer research2022
PGC1α/β Expression Predicts Therapeutic Response to Oxidative Phosphorylation Inhibition in Ovarian Cancer.
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 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Multifunctional biohybrid nanoplatform interferes electron transport chain amplifying mitochondrial metabolism-mediated anti-tumor therapy.Materials today. Bio · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- Sodium-glucose cotransporter 2 inhibitors facilitate cell phenotype conversion of alpha cells through progenitors to beta cells by activating Ppargc1α in diabetic mice.Chinese medical journal · 2026Article
- Role of mitochondrial dysfunction in muscle wasting in cancer cachexia: a narrative review.Journal of translational medicine · 2026Review
- Impairment of oxidative metabolism compromises Rad51 recruitment and potentiates PARP inhibitor effectiveness in ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Subcellular Stress Markers in Epithelial Ovarian Cancer.International journal of molecular sciences · 2025Review
- Patient-derived xenograft models: Current status, challenges, and innovations in cancer research.Genes & diseases · 2025Review
- MRPL13 enhances mitochondrial function and promotes tumor progression in ovarian cancer by inhibiting mPTP opening via SLC25A6.Cell death & disease · 2025Article
- Proteomic Analysis of ARID1A-Deficient Ovarian Clear Cell Carcinoma Cells Reveals Differential Mitochondria ETC Subunit Abundances and Targetable Mitochondrial Pathways.International journal of molecular sciences · 2025Article
- Role of PGC-1α in the proliferation and metastasis of malignant tumors.Journal of molecular histology · 2025Review
- Characteristics of Oxidative Phosphorylation-Related Subtypes and Construction of a Prognostic Signature in Ovarian Cancer.Current gene therapy · 2025Article
- Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer.Journal of translational medicine · 2024Review
- Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- Mitochondrial inhibitors: a new horizon in breast cancer therapy.Frontiers in pharmacology · 2024Review
- From metabolism to malignancy: the multifaceted role of PGC1α in cancer.Frontiers in oncology · 2024Review
- Anti-leukemia effects of omipalisib in acute myeloid leukemia: inhibition of PI3K/AKT/mTOR signaling and suppression of mitochondrial biogenesis.Cancer gene therapy · 2023Article
- A traditional gynecological medicine inhibits ovarian cancer progression and eliminates cancer stem cells via the LRPPRC-OXPHOS axis.Journal of translational medicine · 2023Article
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Authors and funding
21 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancer is the deadliest gynecologic cancer, and novel therapeutic options are crucial to improve overall survival. Here we provide evidence that impairment of oxidative phosphorylation (OXPHOS) can help control ovarian cancer progression, and this benefit correlates with expression of the two mitochondrial master regulators PGC1α and PGC1β. In orthotopic patient-derived ovarian cancer xenografts (OC-PDX), concomitant high expression of PGC1α and PGC1β (PGC1α/β) fostered a unique transcriptional signature, leading to increased mitochondrial abundance, enhanced tricarboxylic acid cycling, and elevated cellular respiration that ultimately conferred vulnerability to OXPHOS inhibition. Treatment with the respiratory chain complex I inhibitor IACS-010759 caused mitochondrial swelling and ATP depletion that consequently delayed malignant progression and prolonged the lifespan of high PGC1α/β-expressing OC-PDX-bearing mice. Conversely, low PGC1α/β OC-PDXs were not affected by IACS-010759, thus pinpointing a selective antitumor effect of OXPHOS inhibition. The clinical relevance of these findings was substantiated by analysis of ovarian cancer patient datasets, which showed that 25% of all cases displayed high PGC1α/β expression along with an activated mitochondrial gene program. This study endorses the use of OXPHOS inhibitors to manage ovarian cancer and identifies the high expression of both PGC1α and β as biomarkers to refine the selection of patients likely to benefit most from this therapy. SIGNIFICANCE: OXPHOS inhibition in ovarian cancer can exploit the metabolic vulnerabilities conferred by high PGC1α/β expression and offers an effective approach to manage patients on the basis of PGC1α/β expression.
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