Lu Dingci, Xia Bingqian, Feng Tianquan, Qi Gui, Ma Zhaowu
The First Affiliated Hospital of Yangtze University, Yangtze University, Nanhuan Road 1, Jingzhou 434023, China.
School of Basic Medicine, Health Science Center, Yangtze University, Nanhuan Road 1, Jingzhou 434023, China.
Biomolecules. 2025 May 2;15(5):659. doi: 10.3390/biom15050659.
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.
癌症在全球范围内长期流行，构成了重大的公共卫生挑战，因此凸显了开发能够解释肿瘤固有异质性的治疗模型的紧迫性。在此背景下，癌症类器官已成为研究肿瘤生物学的有力工具，为深入了解肿瘤微环境中的复杂相互作用提供了有价值的见解。与此同时，研究越来越集中在程序性细胞死亡（RCD）的非凋亡形式上，包括铁死亡、焦亡和坏死性凋亡，这些形式对癌症的发生和发展具有关键影响。癌症类器官不仅概括了原始肿瘤的遗传和表型异质性，还能更精确地研究非凋亡性RCD在肿瘤学中的作用。本综述探讨了癌症类器官在阐明RCD潜在分子机制及其对癌症生物学和治疗反应的影响方面的效用。通过综合近期研究结果，强调了类器官模型在揭示非凋亡性RCD复杂细节方面的重要作用。此外，强调了未来研究的有前景方向，旨在加深我们对这些途径及其治疗潜力的理解。将类器官模型整合到铁死亡、焦亡和坏死性凋亡的研究中，为致癌机制提供了新的见解，并促进了靶向治疗策略的开发。通过将癌症类器官与人类病理生理学联系起来，这种方法不仅为剖析致癌途径提供了一个变革性框架，还能够设计出选择性靶向非凋亡性RCD潜在分子机制的精准疗法。
