Translating ferroptosis into oncology: challenges, opportunities and future directions
Cet article examine les principaux obstacles qui freinent l'utilisation de la ferroptose en cancérologie (limites pharmacologiques, hétérogénéité intratumorale, contraintes immunitaires et microenvironnementales, lacunes concernant les modèles précliniques actuels...), identifie les futurs axes de recherche puis propose une feuille de route pour intégrer les thérapies basées sur la ferroptose dans la pratique clinique
Ferroptosis is an oxidative, lipid peroxidation-driven form of regulated cell death that occurs when antioxidant and organelle-protective systems are compromised. Increasing evidence implicates ferroptosis as a process that can exert both tumour-suppressive and tumour-promoting effects depending on cellular context at multiple stages of cancer evolution (from tumour initiation to metastatic colonization), sparking substantial interest in therapeutically exploiting this mechanism of cell death. Yet, despite rapid preclinical progress, clinical translation of ferroptosis-based strategies remains nascent. In this Review, we examine the major barriers to translation, including pharmacological limitations, tumour-intrinsic heterogeneity, microenvironmental and immune constraints, and gaps in current preclinical modelling. We also highlight emerging opportunities such as new ferroptosis-inducing agents, biomarker-guided patient selection and rational combinations with chemotherapy, radiotherapy, targeted agents or immunotherapies. Finally, we outline a translational roadmap for integrating ferroptosis-based therapies into oncology practice. By defining key challenges and future directions, this Review aims to position ferroptosis as a viable therapeutic paradigm and to accelerate progress towards clinical application.
Nature Reviews Clinical Oncology , article en libre accès, 2026