The Role of Cancer Organoids in Ferroptosis, Pyroptosis, and Necroptosis: Functions and Clinical Implications.

The enduring prevalence of cancer worldwide constitutes a significant public health challenge, thereby emphasizing the imperative for the development of therapeutic models capable of accounting for the heterogeneity inherent in tumors. In this context, cancer organoids have emerged as powerful tools for studying tumor biology, providing valuable insights into the complex interactions within the tumor microenvironment. Concurrently, research is increasingly focused on non-apoptotic forms of regulated cell death (RCD)-including ferroptosis, pyroptosis, and necroptosis-which exert pivotal influences on cancer development and progression. Cancer organoids not only recapitulate the genetic and phenotypic heterogeneity of the original tumors but also enable more precise investigations into the roles of non-apoptotic RCDs within oncology. This review explores the utility of cancer organoids in delineating the molecular mechanisms underlying RCDs and their implications for cancer biology and treatment responses. By synthesizing recent research findings, it highlights the essential role of organoid models in uncovering the intricate details of non-apoptotic RCDs. Furthermore, it emphasizes promising directions for future research that aim to deepen our understanding of these pathways and their therapeutic potential. The integration of organoid models into investigations of ferroptosis, pyroptosis, and necroptosis provides novel insights into oncogenic mechanisms and facilitates the development of targeted therapeutic strategies. By bridging cancer organoids with human pathophysiology, this approach not only provides a transformative framework for dissecting oncogenic pathways but also enables the design of precision therapeutics that selectively target the molecular machinery underlying non-apoptotic RCDs.