NCOA4介导的铁自噬在卵巢癌铂耐药中的作用及靶向策略

doi:10.3760/cma.j.cn371439-20260409-00108

摘要/Abstract

摘要：

铂耐药是晚期卵巢癌治疗失败的主因。铁代谢重编程成为耐药研究新焦点，其中核受体共激活因子4（NCOA4）介导的铁自噬为核心通路。基于最新证据，笔者提出NCOA4“护盾与利剑”双重模型：耐药形成期，NCOA4通过IRP2-NCOA4轴供铁，支持RRM2介导的DNA修复，充当保护性“护盾”；而在特定干预下，其过度激活会升高不稳定铁池、突破抗氧化阈值，诱发铁死亡，转为“利剑”。据此提出“时序性”策略——先抑“护盾”增敏化疗，后激“利剑”清除耐药细胞，为逆转耐药提供新方向。

关键词: 卵巢肿瘤, 铂耐药, 铁死亡, 铁自噬, NCOA4, RRM2

Abstract:

Platinum resistance is the leading cause of treatment failure in advanced ovarian cancer. Iron metabolic reprogramming has emerged as a new focus in drug resistance research， with nuclear receptor coactivator 4 （NCOA4）-mediated ferritinophagy being a core pathway. Based on the latest evidence， a "shield and sword" dual model of NCOA4 is proposed： during the drug resistance formation period， NCOA4 supplies iron via the IRP2-NCOA4 axis to support RRM2-mediated DNA repair， acting as a protective "shield"； under specific interventions， its overactivation elevates the labile iron pool， exceeds antioxidant thresholds， and triggers ferroptosis， turning into a lethal "sword." Accordingly， a "sequential" strategy is proposed—first inhibiting the "shield" to sensitize chemotherapy， then activating the "sword" to eliminate the drug-resistant cells—offering a new direction for reversing platinum resistance.

Key words: Ovarian neoplasms, Platinum resistance, Ferroptosis, Ferritinophagy, NCOA4, RRM2

钱文宇, 杨秀梅. NCOA4介导的铁自噬在卵巢癌铂耐药中的作用及靶向策略[J]. 国际肿瘤学杂志, 2026, 53(11): 694-698.

Qian Wenyu, Yang Xiumei. Role of NCOA4-mediated ferritinophagy in platinum resistance of ovarian cancer and targeted strategies[J]. Journal of International Oncology, 2026, 53(11): 694-698.

图/表 2

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