Role of NCOA4-mediated ferritinophagy in platinum resistance of ovarian cancer and targeted strategies

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

Abstract

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

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.

Figures/Tables 2

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