Liu Chunyan, Liu Wenting, Huang Jun, Wu Zhaoying, Li Wenhui, Chen Bo, Yang Yanjun, Lin Hong, Xu Ying
Department of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, People's Republic of China.
Medical Department, China-Japan Friendship Hospital, Beijing, People's Republic of China.
Cancer Manag Res. 2025 Aug 19;17:1707-1722. doi: 10.2147/CMAR.S538281. eCollection 2025.
Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies due to its asymptomatic progression, frequent late-stage diagnosis, and high rates of chemoresistance and recurrence. Beyond genetic alterations, recent studies highlight the central role of metabolic reprogramming in driving OC initiation, progression, and therapy resistance. OC cells exhibit dynamic metabolic reprogramming, enabling dynamic shifts between glycolysis and oxidative phosphorylation depending on environmental conditions and treatment pressures. In this review, we synthesize current understanding of key metabolic pathways altered in ovarian tumors, including enhanced aerobic glycolysis, glutamine addiction, dysregulated lipid metabolism, and mitochondrial adaptations. These metabolic shifts support rapid proliferation, redox homeostasis, immune evasion, and metastatic potential. We also explore how the metabolic landscape of OC is shaped by interactions with the tumor microenvironment, particularly through crosstalk with immune cells, cancer-associated fibroblasts, and adipocytes. Importantly, metabolic adaptations have been implicated in the emergence of cancer stem-like cells and in the development of resistance to platinum-based chemotherapy and PARP inhibitors. We also further discuss emerging therapeutic strategies targeting metabolic vulnerabilities, as well as combinatorial approaches integrating metabolic therapy with immunotherapy and DNA damage repair inhibition. Finally, we highlight how advances in metabolomics and spatial profiling are improving our ability to map metabolic heterogeneity and guide precision therapies in OC. This review underscores metabolic plasticity as a promising therapeutic vulnerability for overcoming drug resistance and improving outcomes in OC patients.
卵巢癌（OC）仍然是最致命的妇科恶性肿瘤之一，因为它进展时无症状、晚期诊断频繁，且化疗耐药和复发率高。除了基因改变外，最近的研究强调了代谢重编程在驱动OC起始、进展和治疗耐药中的核心作用。OC细胞表现出动态的代谢重编程，根据环境条件和治疗压力，能够在糖酵解和氧化磷酸化之间进行动态转换。在这篇综述中，我们综合了目前对卵巢肿瘤中改变的关键代谢途径的理解，包括增强的有氧糖酵解、谷氨酰胺成瘾、脂质代谢失调和线粒体适应。这些代谢转变支持快速增殖、氧化还原稳态、免疫逃逸和转移潜能。我们还探讨了OC的代谢格局如何通过与肿瘤微环境的相互作用而形成，特别是通过与免疫细胞、癌症相关成纤维细胞和脂肪细胞的串扰。重要的是，代谢适应与癌症干细胞样细胞的出现以及对铂类化疗和PARP抑制剂的耐药性发展有关。我们还进一步讨论了针对代谢脆弱性的新兴治疗策略，以及将代谢疗法与免疫疗法和DNA损伤修复抑制相结合的联合方法。最后，我们强调了代谢组学和空间分析的进展如何提高我们绘制代谢异质性图谱和指导OC精准治疗的能力。这篇综述强调了代谢可塑性作为克服耐药性和改善OC患者预后的一个有前景的治疗脆弱性。
