Organoid models of ovarian cancer: resolving immune mechanisms of metabolic reprogramming and drug resistance

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 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.

Язык: Английский

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Zengmian Yiliu formula suppresses cell cycle in immune-rich ovarian cancer patient-derived organoids

Phytomedicine, Год журнала: 2025, Номер 141, С. 156721 - 156721

Опубликована: Апрель 5, 2025

Язык: Английский

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Advancing precision medicine: strategies from organoids research

Cell organoid (Print), Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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The pros and cons of mechanical dissociation and enzymatic digestion in patient-derived organoid cultures for solid tumor

Cell organoid (Print), Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Patient-derived organoids (PDOs) are revolutionizing cancer research, serving as invaluable models for tumor biology and therapeutic screening. The fidelity applicability of these fundamentally shaped by the tissue dissociation techniques employed, namely mechanical enzymatic digestion. This comprehensive review delves into nuances two methods, scrutinizing their effects on solid organoid properties, including stemness, heterogeneity, long-term culturing. We discuss advantages limitations each technique, with a focus impact microenvironment preservation, application in drug screening modeling. Moreover, we examine how recent technological breakthroughs have bolstered efficiency scalability production through methods. Our analysis is designed to assist researchers choosing optimal strategy research objectives fuel evolution organoid-based models.

Язык: Английский

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Research progress of immune checkpoint inhibitors in ovarian cancer

Exploration of Immunology, Год журнала: 2024, Номер unknown, С. 853 - 870

Опубликована: Дек. 18, 2024

Ovarian cancer is the deadliest malignant tumor in female reproductive system. Despite advancements standard treatments such as debulking surgery and platinum-based chemotherapy, overall survival rate remains low. The emergence of targeted therapies, including Poly(ADP-ribose) polymerase (PARP) inhibitors anti-angiogenic agents, has provided new avenues for treatment. However, drug resistance disease heterogeneity continue to pose significant challenges. Immune checkpoint (ICIs), an emerging therapeutic approach, primarily target programmed cell death protein 1 (PD-1)/programmed ligand (PD-L1) cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways restore anti-tumor immune responses. Although ICIs have shown efficacy other malignancies, their effectiveness ovarian limited, with a response only 10–15% monotherapy. Recent studies focused on combining or PARP enhance outcomes. This article reviews progress cancer, monotherapy combination treatment strategies, explores targets strategies aimed at improving patient prognosis achieving personalized By gaining deeper understanding microenvironment its evasion mechanisms, there hope developing more effective options future, ultimately rates quality life patients.

Язык: Английский

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Enterolactone combined with m6A Reader IGF2BP3 inhibits Malignant Angiogenesis and Disease Progression in Ovarian Cancer

Phytomedicine, Год журнала: 2024, Номер 136, С. 156343 - 156343

Опубликована: Дек. 21, 2024

Язык: Английский

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