Organoid models of ovarian cancer: resolving immune mechanisms of metabolic reprogramming and drug resistance DOI Creative Commons
Lanyue Zhang,

Jiangnan Zhao,

Changqing Su

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

Metabolic reprogramming is a hallmark of ovarian cancer, enabling tumor progression, immune evasion and drug resistance. The microenvironment (TME) further shapes metabolic adaptations, cancer cells to withstand hypoxia nutrient deprivation. While organoid models provide physiologically relevant platform for studying these processes, they still lack vascular components, limiting their ability fully recapitulate metabolism responses. In this study, we investigated the key mechanisms involved in focusing on glycolysis, lipid amino acid metabolism. We integrated metabolomic analyses sensitivity assays explore metabolic-TME interactions using patient-derived, adult stem cell-derived iPSC-derived organ tissues. Among these, found that play central role progression chemotherapy identified methylglyoxal (MGO)-mediated BRCA2 dysfunction as driver escape, sphingolipid signaling proliferation kynurenine CD8+ T cell suppression. addition, PI3K/AKT/mTOR Wnt/β-catenin pathways promote chemoresistance through adaptation. By elucidating link between evasion, study identifies vulnerabilities potential targets cancer. Our findings support development metabolically targeted therapies increase utility organoid-based precision medicine models.

Language: Английский

Organoid models of ovarian cancer: resolving immune mechanisms of metabolic reprogramming and drug resistance DOI Creative Commons
Lanyue Zhang,

Jiangnan Zhao,

Changqing Su

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

Metabolic reprogramming is a hallmark of ovarian cancer, enabling tumor progression, immune evasion and drug resistance. The microenvironment (TME) further shapes metabolic adaptations, cancer cells to withstand hypoxia nutrient deprivation. While organoid models provide physiologically relevant platform for studying these processes, they still lack vascular components, limiting their ability fully recapitulate metabolism responses. In this study, we investigated the key mechanisms involved in focusing on glycolysis, lipid amino acid metabolism. We integrated metabolomic analyses sensitivity assays explore metabolic-TME interactions using patient-derived, adult stem cell-derived iPSC-derived organ tissues. Among these, found that play central role progression chemotherapy identified methylglyoxal (MGO)-mediated BRCA2 dysfunction as driver escape, sphingolipid signaling proliferation kynurenine CD8+ T cell suppression. addition, PI3K/AKT/mTOR Wnt/β-catenin pathways promote chemoresistance through adaptation. By elucidating link between evasion, study identifies vulnerabilities potential targets cancer. Our findings support development metabolically targeted therapies increase utility organoid-based precision medicine models.

Language: Английский

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