Lin Jin-Fei, Wang Ting-Ting, Huang Ren-Ze, Tan Yue-Tao, Chen Dong-Liang, Ju Huai-Qiang
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China.
Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, Guangzhou, PR China.
Cell Mol Immunol. 2025 Jul 28. doi: 10.1038/s41423-025-01329-z.
PANoptosis, a newly defined inflammatory programmed cell death, plays key roles in tumor development and progression. This process involves the assembly of PANoptosome complexes under various stimuli, which activate multiple cell death pathways simultaneously. By integrating key sensors and effector molecules, PANoptosis enhances immunogenic cell death while counteracts immune evasion mechanisms. This review focuses on current research of PANoptosis in cancer. Clinically, PANoptosis-related signatures show clinical value for predicting patient survival, discerning tumor immune microenvironment (TIME) characteristics and evaluating the therapeutic response. Mechanistically, complex signaling networks regulate PANoptosis, which in turn influences tumor behavior through dynamic interactions with TIME components. Therapeutically, targeting PANoptosis-related pathways, including nanomedicine approaches, demonstrate encouraging preclinical results. Particularly, combining PANoptosis modulation with radiotherapy, chemotherapy, or immunotherapy enhances anti-tumor efficacy. These findings position PANoptosis as a promising therapeutic target for reshaping TIME, overcoming treatment resistance, and improving cancer outcomes. Future research will focus on elucidating context-dependent PANoptosome regulation and translating these insights into precision oncology strategies.
PAN细胞焦亡是一种新定义的炎症性程序性细胞死亡，在肿瘤发生和发展中起关键作用。这一过程涉及在各种刺激下PAN细胞焦亡体复合物的组装，其可同时激活多种细胞死亡途径。通过整合关键传感器和效应分子，PAN细胞焦亡增强免疫原性细胞死亡，同时对抗免疫逃逸机制。本综述聚焦于目前癌症中PAN细胞焦亡的研究。临床上，与PAN细胞焦亡相关的特征在预测患者生存、识别肿瘤免疫微环境（TIME）特征及评估治疗反应方面具有临床价值。从机制上讲，复杂的信号网络调节PAN细胞焦亡，而PAN细胞焦亡又通过与TIME成分的动态相互作用影响肿瘤行为。在治疗方面，靶向与PAN细胞焦亡相关的途径，包括纳米医学方法，已显示出令人鼓舞的临床前结果。特别是，将PAN细胞焦亡调节与放疗、化疗或免疫疗法相结合可提高抗肿瘤疗效。这些发现使PAN细胞焦亡成为重塑TIME、克服治疗耐药性及改善癌症治疗结果的一个有前景的治疗靶点。未来的研究将集中于阐明依赖于背景的PAN细胞焦亡体调节，并将这些见解转化为精准肿瘤学策略。
