Ferroptosis-Based Therapeutic Strategies toward Precision Medicine for Cancer

Abstract

Ferroptosis is a type of iron-dependent programmed cell death characterized by the dysregulation of iron metabolism and the accumulation of lipid peroxides. This nonapoptotic mode of cell death is implicated in various physiological and pathological processes. Recent findings have underscored its potential as an innovative strategy for cancer treatment, particularly against recalcitrant malignancies that are resistant to conventional therapies. This article focuses on ferroptosis-based therapeutic strategies for precision cancer treatment, covering the molecular mechanisms of ferroptosis, four major types of ferroptosis inducers and their inhibitory effects on diverse carcinomas, the detection of ferroptosis by fluorescent probes, and their implementation in image-guided therapy. These state-of-the-art tactics have manifested enhanced selectivity and efficacy against malignant carcinomas. Given that the administration of ferroptosis in cancer therapy is still at a burgeoning stage, some major challenges and future perspectives are discussed for the clinical translation of ferroptosis into precision cancer treatment. ■ SIGNIFICANCE • The potential of ferroptosis as an innovative strategy for precision cancer therapy is highlighted. • Recent advances are discussed from three perspectives: molecular mechanism and regulation, anti-cancer ferroptosis inducers, and ferroptosis probes for image-guided therapy. • The strengths and weaknesses of ferroptosis modulators and probes are analyzed in terms of current progress and technical barriers. • Future perspectives are emphasized to advance ferroptosis-based therapies toward clinical use for cancer treatment.

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

“…14 Ferroptosis-inducing therapies have emerged as a crucial strategy in oncology, with ongoing advancements in the development and study of various small molecule drugs targeting ferroptosis-regulating pathways. 15 This review provides an overview of the regulatory mechanisms of ferroptosis and delves into the mechanisms of traditional small molecule ferroptosis inducers and their effects on various tumors. It also highlights the recent progress in inducing ferroptosis through innovative methods such as PROTACs, PDT, SDT, and nanomaterials.…”