Targeting pyroptosis, ferroptosis, and cuproptosis: An updated view of regulated cell death pathways for cancer therapy

作者：Jing Zhao, Xueqing Du, W. Fang, Yin Yan, Zinan Li, Hongxia Zhu, Binglin Yue · 发表于：Eurasian Journal of Medicine and Oncology · 年份：2026 · DOI：10.36922/ejmo026260298

Introduction: Cancer treatment has long relied on inducing apoptosis; however, tumors frequently develop resistance through apoptosis-evasion mechanisms, leading to recurrence and metastasis. In recent years, three emerging forms of programmed cell death—pyroptosis, ferroptosis, and cuproptosis—have attracted intense interest. Thanks to their distinct molecular pathways and strong immunogenic properties, they offer promising ways to overcome the limitations of traditional therapies. These mechanisms, driven by inflammatory signaling or dysregulation of metal ions (iron or copper), trigger mitochondrial dysfunction, lipid peroxidation, or membrane pore formation. Beyond directly killing tumor cells, they release damage-associated molecular patterns that activate immunogenic cell death. This process reshapes the tumor microenvironment and significantly enhances the efficacy of immune checkpoint inhibitors. Objective: This review systematically summarizes the molecular regulation, network interactions, and therapeutic advances of these three novel cell death pathways, providing new theoretical foundations and potential translational strategies for treating refractory cancers. Conclusion: Pyroptosis, ferroptosis, and cuproptosis represent interconnected, non-apoptotic cell death pathways with substantial potential to overcome therapeutic resistance, remodel the immunosuppressive tumor microenvironment, and enhance responses to immune checkpoint blockade. Further mechanistic valid...