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MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1573686
This article is part of the Research Topic The Role of Metabolic Reprogramming in Tumor Therapy View all 7 articles
Organoid models of ovarian cancer: resolving immune mechanisms of metabolic reprogramming and drug resistance
Provisionally accepted- 1 School of Clinical Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, China
- 2 Department of Preventive Medicine,Southwest Medical University, Luzhou, China
- 3 Sichuan Provincial Center for Gynecology and Breast Diseases (Gynecology), Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China
Metabolic reprogramming is a hallmark of ovarian cancer, enabling tumour progression, immune evasion and drug resistance. The tumour microenvironment (TME) further shapes metabolic adaptations, enabling cancer cells to withstand hypoxia and nutrient deprivation. While organoid models provide a physiologically relevant platform for studying these processes, they still lack immune and vascular components, limiting their ability to fully recapitulate tumour metabolism and drug responses. In this study, we investigated the key metabolic mechanisms involved in ovarian cancer progression, focusing on glycolysis, lipid metabolism and amino acid metabolism. We integrated metabolomic analyses and drug sensitivity assays to explore metabolic-TME interactions using patient-derived, adult stem cell-derived and iPSC-derived organ tissues. Among these, we found that glycolysis, lipid metabolism and amino acid metabolism play a central role in tumour progression and chemotherapy resistance. We identified methylglyoxal (MGO)-mediated BRCA2 dysfunction as a driver of immune escape, a role for sphingolipid signalling in tumour proliferation and a role for kynurenine metabolism in CD8+ T cell suppression. In addition, PI3K/AKT/mTOR and Wnt/β-catenin pathways promote chemoresistance through metabolic adaptation. By elucidating the link between metabolic reprogramming and immune evasion, this study identifies key metabolic vulnerabilities and potential drug targets in ovarian cancer. Our findings support the development of metabolically targeted therapies and increase the utility of organoid-based precision medicine models.
Keywords: ovarian cancer, Organoid, Drug Resistance, metabolic reprogramming, Molecular mechanisms, immune escape, personalized therapy
Received: 09 Feb 2025; Accepted: 04 Mar 2025.
Copyright: © 2025 Zhang, Zhao, Su, Wu, Jiang, Chi and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hao Chi, School of Clinical Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, China
Qin Wang, Sichuan Provincial Center for Gynecology and Breast Diseases (Gynecology), Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China
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