Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

Abstract: Ferroptosis, a unique form of programmed cell death, is initiated by an excess of iron accumulation and lipid peroxidation-induced damage. There is a growing body of evidence indicating that ferroptosis plays a critical role in the advancement of tumors. The increased metabolic activity and higher iron levels in tumor cells make them particularly vulnerable to ferroptosis. As a result, the targeted induction of ferroptosis is becoming an increasingly promising approach for cancer treatment. This review offers an overview of the regulatory mechanisms of ferroptosis, delves into the mechanism of action of traditional small molecule ferroptosis inducers and their effects on various tumors. In addition, the latest progress in inducing ferroptosis using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic therapy (SDT) and nanomaterials is summarized. Finally, this review discusses the challenges and opportunities in the development of ferroptosis-inducing agents, focusing on discovering new targets, improving selectivity, and reducing toxic and side effects. Keywords: ferroptosis inducers, small molecules, PROTACs, PDT, SDT, nanomaterials