Ferroptosis as a Therapeutic Strategy in Cancer: From Mechanisms toClinical Applications

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a promising therapeutic target in cancer treatment. This review critically evaluates recent advances in understanding the molecular mechanisms of ferroptosis and its application in oncology. We analyzed preclinical and clinical studies published between 2015 and 2025, sourced from major scientific databases including PubMed, Scopus, and Web of Science. Key findings highlight an expanding range of small molecules, natural compounds, and nanomedicines that induce or inhibit ferroptosis through pathways involving GPX4, SLC7A11, FSP1, and iron metabolism. Ferroptosis has been shown to enhance the efficacy of chemotherapy, radiotherapy, and immunotherapy while overcoming mechanisms of drug resistance. Despite these advances, translational challenges, such as off-target toxicity, tumor heterogeneity, and limited biomarkers for patient selection, remain. This review emphasizes the therapeutic potential of ferroptosis modulation and outlines future directions for integrating ferroptosis-targeted strategies into precision cancer therapy