恶性肿瘤对全球健康构成了重大威胁，寻找有效治疗方案成为当务之急。尽管存在多种治疗方法，包括手术、放射治疗、化学治疗、免疫治疗和联合疗法，但仍然需要开发能够以调控细胞死亡通路为靶点的治疗方案，以消除癌细胞同时保护正常细胞。碱性细胞死亡是一种依赖于pH值的细胞死亡过程，由小分子化合物JTC801引发，已被鉴定为一种治疗恶性肿瘤的新方法，尤其在胰腺癌中表现出了潜力。两个主要的信号通路，即NF-κB-CA9通路和ATP6V0D1-STAT3通路，对碱性细胞死亡的诱导起到重要作用。本综述总结了碱性细胞死亡信号、机制和调控的最新进展，并探讨了其在药物抵抗、炎症和免疫方面的上下文依赖效应。通过对细胞死亡机制多样性和可塑性的深入理解，这些信息有望为设计更加有效的抗肿瘤疗法提供指导。版权所有 © 2023 Chen, Kang, Liu and Tang.

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.Copyright © 2023 Chen, Kang, Liu and Tang.