Ferroptosis represents a rapidly advancing area within cancer research, distinguished by its iron-dependent lipid peroxidation mechanism that diverges significantly from traditional forms of cell death. This process has garnered considerable attention for its ability to selectively target and eradicate cancer cells, particularly those resistant to established therapies. Despite the promise shown in preclinical models, crucial barriers remain in fully elucidating the intricate regulatory networks that modulate ferroptosis within diverse tumor contexts. Key questions also persist regarding the identification of reliable, clinically actionable biomarkers and the translation of basic discoveries into therapeutic interventions for patients.

Recent studies have significantly expanded the knowledge of the molecular underpinnings of ferroptosis, highlighting the roles of lipid metabolism, iron homeostasis, and antioxidant systems in this unique cell death pathway. Innovations in drug discovery have led to the design of potent inducers and modulators of ferroptosis, while early-stage clinical trials have begun exploring their therapeutic efficacy. A growing body of evidence also points to the dynamic influence of the tumor microenvironment and the potential for synergistic combinations with established cancer treatments, such as immunotherapy and radiotherapy. Nonetheless, substantial gaps hinder clinical application, including technical limitations in monitoring ferroptosis, tumor heterogeneity, and insufficient integration of ferroptosis-based approaches into therapeutic pipelines.

This Research Topic aims to advance the comprehensive understanding of ferroptosis in cancer biology and to accelerate the translation of mechanistic insights into innovative therapeutic strategies. The primary objectives include unraveling context-dependent regulatory axes, elucidating how tumor heterogeneity and the microenvironment shape ferroptosis sensitivity, identifying novel biomarkers, developing effective inducers and combination therapies, and addressing the challenges that impede clinical implementation. Central questions pertain to the mechanisms sustaining ferroptosis resistance, the scalability of ferroptosis-targeting therapeutics, and optimizing patient selection criteria for future clinical trials.

To gather further insights in the landscape of ferroptosis-focused cancer therapy, this Research Topic welcomes cutting-edge research and expert perspectives that specifically address embedded mechanistic, translational, and therapeutic dimensions, while recognizing the technical and clinical constraints of the field. We encourage submissions on the following themes:

Molecular and metabolic regulation of ferroptosis in cancer

Tumor heterogeneity and microenvironmental modulation of ferroptosis sensitivity

Development, optimization, and delivery of ferroptosis inducers

Advances in biomarker discovery and updates from preclinical/clinical trials

Synergy between ferroptosis-based strategies and conventional cancer therapies (e.g., immunotherapy, radiotherapy)

Appendix: Original and review articles, brief research reports, and perspectives are welcome.

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Ferroptosis in cancer: From regulatory networks to therapeutic breakthroughs