Ferroptosis: A new horizon in cancer therapy

Abstract Ferroptosis is an iron-catalyzed form of regulated cell death mediated by lipid peroxidation. Novel ferroptosis-based therapeutic strategies could selectively target core pathways associated with the proliferation and survival of malignant tumors, not only directly inducing tumor cell death but also overcoming resistance to conventional therapies, paving a new path for precision cancer treatment. Ferroptosis suppresses tumor progression through lethal lipid peroxidation, yet is co-opted by cancers through antioxidant adaptations. This review highlights the dual role of ferroptosis in tumor biology and explores the dynamic interplay between ferroptosis and the tumor microenvironment to modulate both immunogenic cell death and immunosuppressive signaling. We discuss the therapeutic potential of ferroptosis induction through synergistic integration with chemotherapy, targeted therapy, radiotherapy, hyperthermia therapy, and immunotherapy to simultaneously suppress tumor progression, overcome resistance mechanisms, and potentiate antitumor immunity, thereby offering innovative strategies to address treatment-refractory malignancies. Challenges include identifying predictive biomarkers, developing tumor-selective ferroptosis inducers, and modulating ferroptosis–immune interactions within the tumor microenvironment. By addressing these issues, ferroptosis has the potential to overcome treatment-resistant and immune-evasive tumors, reshaping oncology therapeutics.