Chen Fangquan, Kang Rui, Liu Jiao, Tang Daolin
The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Surgery, UT Southwestern Medical Center, Dallas, TX, United States.
Front Cell Dev Biol. 2023 Aug 4;11:1213995. doi: 10.3389/fcell.2023.1213995. eCollection 2023.
Malignant tumors represent a major threat to global health and the search for effective treatments is imperative. While various treatments exist, including surgery, radiotherapy, chemotherapy, immunotherapy and combination therapies, there remains a need to develop therapies that target regulated cell death pathways to eliminate cancer cells while preserving normal cells. Alkaliptosis, a pH-dependent cell death process triggered by the small molecular compound JTC801, has been identified as a novel approach for malignant tumor treatment, particularly in pancreatic cancer. Two major signaling pathways, the NF-κB-CA9 pathway and the ATP6V0D1-STAT3 pathway, contribute to the induction of alkaliptosis. This review summarizes recent developments in our understanding of alkaliptosis signals, mechanisms, and modulation, and explores its context-dependent effects on drug resistance, inflammation, and immunity. By providing a deeper understanding of the heterogeneity and plasticity of cell death mechanisms, this information holds promise for informing the design of more effective anti-tumor therapies.
恶性肿瘤是全球健康的重大威胁，因此寻找有效的治疗方法势在必行。虽然存在多种治疗方法，包括手术、放疗、化疗、免疫疗法及联合疗法，但仍需要开发靶向程序性细胞死亡途径的疗法，以消除癌细胞同时保留正常细胞。碱中毒性坏死是一种由小分子化合物JTC801触发的pH依赖性细胞死亡过程，已被确定为恶性肿瘤治疗的一种新方法，尤其是在胰腺癌治疗中。两条主要信号通路，即NF-κB-CA9通路和ATP6V0D1-STAT3通路，促成了碱中毒性坏死的诱导。本文综述了我们对碱中毒性坏死信号、机制和调节的最新认识进展，并探讨了其对耐药性、炎症和免疫的背景依赖性影响。通过更深入地了解细胞死亡机制的异质性和可塑性，这些信息有望为设计更有效的抗肿瘤疗法提供参考。
