Targeting ferroptosis pathways in cancer: Emerging molecular targets and therapeutic strategies

Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, has emerged as a crucial tumor suppressive mechanism and a promising therapeutic target in oncology. This review synthesizes the current understanding of its core molecular machinery, encompassing lipid metabolism, iron homeostasis, and multi-layered cellular defense systems. We highlight the unique metabolic and genetic vulnerabilities that render specific cancer cell types intrinsically susceptible to ferroptosis. Furthermore, we discuss the dynamic propagation of ferroptotic signals within the tumor microenvironment and their complex immunomodulatory effects. Central to this review is a strategic framework for targeting ferroptosis, synthesizing recent advances in the development of specific ferroptosis inducers and evaluating their synergistic potential when combined with chemotherapy, radiotherapy, targeted therapy, and immunotherapy. By integrating mechanistic insight with translational perspectives, this work provides a systematic guide for rationally exploiting ferroptosis in cancer treatment.