Targeting Regulated Cell Death Pathways in Cancer: Apoptosis, Ferroptosis, Pyroptosis, and Necroptosis for Therapy

Regulated cell death (RCD) comprises a diverse and expanding set of molecularly defined processes, such as apoptosis, necroptosis, ferroptosis, and pyroptosis, each essential for tissue homeostasis and disease regulation. As the field advances, new mechanisms integrating multiple death pathways continue to emerge. In response, the Nomenclature Committee on Cell Death (NCCD) has established standardized guidelines for defining and interpreting cell death based on morphological, biochemical, and functional criteria. In cancer, disruption of these pathways enables tumor cells to evade death - one of the central hallmarks of malignancy - and contributes to resistance to conventional therapies. Increasing evidence reveals extensive crosstalk among distinct RCD modalities, influencing tumor progression, immune responses, and therapeutic efficacy. Recent advances in the molecular characterization of these pathways have uncovered key regulatory nodes and context-dependent vulnerabilities, providing a foundation for the development of innovative strategies to overcome therapeutic resistance and improve clinical outcomes.

This Research Topic aims to bring together cutting-edge original studies and comprehensive reviews that explore emerging mechanisms of regulated cell death and their translational implications in cancer therapy. Despite significant progress in understanding individual RCD pathways, major challenges remain in effectively targeting these processes in a clinically meaningful and context-specific manner. A central question guiding this issue is: how can regulated cell death pathways be precisely and efficiently modulated to improve cancer treatment? To address this, we seek contributions that not only deepen mechanistic insights but also bridge the gap between basic research and clinical application. Emphasis will be placed on identifying actionable targets, overcoming resistance mechanisms, and developing innovative therapeutic strategies, including rational combination approaches and advanced drug delivery systems.

This Research Topic highlights recent advances in targeting multiple forms of regulated cell death for cancer therapy, with a focus on apoptosis, ferroptosis, pyroptosis, and necroptosis. We welcome submissions addressing key themes such as:

(1) development of therapeutic agents and delivery platforms, including small molecules, nucleic acid–based therapeutics, natural products, antibody–drug conjugates, and nanocarriers;

(2) identification of novel molecular targets and regulatory networks;

(3) progress in preclinical and clinical studies;

(4) combination strategies involving immunotherapy and other treatment modalities;

(5) key fundamental mechanisms regulating sensitivity and resistance to these regulated cell death pathways; and

(6) mechanisms driving therapeutic resistance.

We encourage multidisciplinary contributions spanning molecular and cellular biology, medicinal chemistry, nanotechnology, immunology, pharmacology, clinical oncology, translational research, and bioinformatics.

A wide range of manuscript types is welcome, including Original Research, Reviews, Systematic Reviews, Clinical Trials, Perspectives, Brief Reports, Commentaries, and Opinions.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Registered Report
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: targeted therapies, molecular targets, regulated cell death, drug delivery systems, combined therapies, nanocarriers, nucleic acid therapeutics, apoptosis, ferroptosis, pyroptosis, necroptosis, cancer, therapy resistance

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.