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全程序坏死:抗癌策略的新时代。

PANoptosis: A new era for anti-cancer strategies.

作者信息

Cui Ziheng, Li Yuan, Bi Yao, Li Wenjing, Piao Junjie, Ren Xiangshan

机构信息

Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, China.

Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, China; Department of Anesthesia, Affiliated Hospital of Yanbian University, Yanji, China.

出版信息

Life Sci. 2024 Dec 15;359:123241. doi: 10.1016/j.lfs.2024.123241. Epub 2024 Nov 15.

DOI:10.1016/j.lfs.2024.123241
PMID:39549938
Abstract

Cancer cells possess an extraordinary ability to dodge cell death through various pathways, granting them a form of immortality-a key obstacle in oncotherapy. Thus, it's vital to unravel the intricate mechanisms behind newly discovered types of cell death that drive tumor suppression, going beyond apoptosis alone. The emergence of PANoptosis, a form of cell death intertwining necroptosis, pyroptosis, and apoptosis, offers a fresh perspective, integrating these pathways into one cohesive process. When cells detect damage signals, they assemble PANoptosome complexes that disrupt their balance, trigger immune responses, and lead to their eventual collapse. PANoptosis has been associated with multiple cellular pathways, including ferroptosis. Mitochondrial dysfunction also plays a critical role in sparking and advancing PANoptosis. In this review, we map out the molecular machinery and regulatory web controlling PANoptosis. We explore cutting-edge research and future trends in PANoptosis-centered tumor therapies, spotlighting promising innovations that could amplify cancer treatment effectiveness through harnessing this multifaceted cell death pathway. The development of nanomedicines and nanomaterials provides solutions to the therapeutic challenges of clinical drugs. Developing novel tumor nano-PANoptosis inducers by leveraging the advantages of nanomedicine is of research value. Traditional Chinese medicine (TCM) treatment is characterized by multiple targets, and it has distinct advantages in triggering PANoptosis through multiple pathways. Additionally, photodynamic Therapy (PDT) may offer new insights into promoting PANoptosis in tumor cells by increasing oxidative stress and reactive oxygen species levels. These will establish a solid theoretical groundwork for the development of integrated treatment methodologies.

摘要

癌细胞具有通过各种途径躲避细胞死亡的非凡能力,这赋予了它们一种永生的形式——这是肿瘤治疗中的一个关键障碍。因此,揭示新发现的驱动肿瘤抑制的细胞死亡类型背后的复杂机制至关重要,而不仅仅局限于凋亡。PANoptosis的出现,一种将坏死性凋亡、炎性小体凋亡和凋亡交织在一起的细胞死亡形式,提供了一个全新的视角,将这些途径整合为一个连贯的过程。当细胞检测到损伤信号时,它们会组装PANoptosome复合物,破坏其平衡,触发免疫反应,并导致细胞最终崩溃。PANoptosis与多种细胞途径有关,包括铁死亡。线粒体功能障碍在引发和推进PANoptosis中也起着关键作用。在这篇综述中,我们梳理了控制PANoptosis的分子机制和调控网络。我们探索了以PANoptosis为中心的肿瘤治疗的前沿研究和未来趋势,重点介绍了有望通过利用这种多方面的细胞死亡途径来提高癌症治疗效果的创新方法。纳米药物和纳米材料的发展为临床药物的治疗挑战提供了解决方案。利用纳米医学的优势开发新型肿瘤纳米PANoptosis诱导剂具有研究价值。中医治疗具有多靶点的特点,在通过多种途径触发PANoptosis方面具有独特优势。此外,光动力疗法(PDT)可能通过增加氧化应激和活性氧水平为促进肿瘤细胞中的PANoptosis提供新的见解。这些将为综合治疗方法的发展奠定坚实的理论基础。

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