Metabolic vulnerabilities in ovarian cancer decoding the nexus between nutrient adaptation and therapy resistance

IF 17.1 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of Advanced Research Pub Date : 2026-10-01 Epub Date: 2026-01-18 DOI:10.1016/j.jare.2026.01.047

Xiaoyu Guo, Zongang Liu, Xiaoman Li, Bingzheng Zhou, Jingyi Chen

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引用次数: 0

Abstract

Background

Ovarian cancer (OC) is a leading cause of gynecologic cancer-related mortality, primarily due to frequent therapy resistance and disease recurrence. Growing evidence indicates that metabolic reprogramming serves as a critical adaptive mechanism, allowing cancer cells to survive therapeutic stress.

Aim of review

This review aims to decode the interplay between nutrient adaptation and therapy resistance in OC. It examines how alterations in key metabolic pathways contribute to treatment resilience and disease progression, and explores the potential of targeting metabolic vulnerabilities to improve therapeutic outcomes.

Key scientific concepts of review

We discuss how OC cells utilize metabolic pathways—including glycolysis, OXPHOS, glutamine metabolism, and lipid utilization—to promote survival, DNA repair, and immune evasion. Metabolic plasticity enables shifts between nutrient sources, driving resistance to platinum-based agents, PARP inhibitors, and anti-angiogenic therapies. These adaptations vary across subtypes, such as high-grade serous and clear cell carcinomas, and are influenced by specific mutations. Targeting metabolic enzymes—such as GLS, CPT1, OXPHOS complexes, or NAD⁺ synthesis—offers a promising strategic direction. Metabolic profiling may allow stratification of OC patients and pave the way for precision medicine approaches to overcome treatment resistance.

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卵巢癌的代谢脆弱性解码营养适应和治疗抵抗之间的联系

卵巢癌（OC）是妇科癌症相关死亡的主要原因，主要是由于频繁的治疗抵抗和疾病复发。越来越多的证据表明，代谢重编程是一种关键的适应机制，使癌细胞能够在治疗性应激下存活。本文旨在研究营养适应与治疗抗性之间的相互作用。它研究了关键代谢途径的改变如何促进治疗弹性和疾病进展，并探索了针对代谢脆弱性改善治疗结果的潜力。我们讨论了OC细胞如何利用代谢途径，包括糖酵解、OXPHOS、谷氨酰胺代谢和脂质利用，来促进生存、DNA修复和免疫逃避。代谢可塑性使营养来源之间的转换，驱动对铂基药物，PARP抑制剂和抗血管生成疗法的抗性。这些适应因亚型而异，如高级别浆液性和透明细胞癌，并受特定突变的影响。靶向代谢酶-如GLS， CPT1， OXPHOS复合物或NAD+合成-提供了一个有前途的战略方向。代谢谱分析可以对OC患者进行分层，并为克服治疗耐药性的精准医学方法铺平道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Advanced Research Multidisciplinary-Multidisciplinary

CiteScore

21.60

自引率

0.90%

发文量

280

审稿时长

12 weeks

期刊介绍： Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences. The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.