Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Chin Med J (Engl). 2023 Mar 20;136(6):653-665. doi: 10.1097/CM9.0000000000002239.
Regulated cell death (RCD), including apoptosis, pyroptosis, necroptosis, and ferroptosis, is regulated by a series of evolutionarily conserved pathways, and is required for development and tissue homeostasis. Based on previous genetic and biochemical explorations of cell death subroutines, the characteristics of each are generally considered distinctive. However, recent in-depth studies noted the presence of crosstalk between the different forms of RCD; hence, the concept of PANoptosis appeared. Cancer, a complex genetic disease, is characterized by stepwise deregulation of cell apoptosis and proliferation, with significant morbidity and mortality globally. At present, studies on the different RCD pathways, as well as the intricate relationships between different cell death subroutines, mainly focus on infectious diseases, and their roles in cancer remain unclear. As cancers are characterized by dysregulated cell death and inflammatory responses, most current treatment strategies aim to selectively induce cell death via different RCD pathways in cancer cells. In this review, we describe five types of RCD pathways in detail with respect to tumorigenesis and cancer progression. The potential value of some of these key effector molecules in tumor diagnosis and therapeutic response has also been raised. We then review and highlight recent progress in cancer treatment based on PANoptosis and ferroptosis induced by small-molecule compounds, immune checkpoint inhibitors, and nanoparticles. Together, these findings may provide meaningful evidence to fill in the gaps between cancer pathogenesis and RCD pathways to develop better cancer therapeutic strategies.
程序性细胞死亡（RCD），包括细胞凋亡、细胞焦亡、细胞坏死和铁死亡，是由一系列进化上保守的途径调控的，对于发育和组织稳态是必需的。基于细胞死亡子程序的先前遗传和生化探索，每种细胞死亡的特征通常被认为是独特的。然而，最近的深入研究注意到不同形式的 RCD 之间存在串扰；因此，出现了 PANoptosis 的概念。癌症是一种复杂的遗传疾病，其特征是细胞凋亡和增殖的逐步失调，在全球范围内具有显著的发病率和死亡率。目前，对不同 RCD 途径的研究，以及不同细胞死亡子程序之间的复杂关系，主要集中在传染病上，它们在癌症中的作用尚不清楚。由于癌症的特征是细胞死亡和炎症反应失调，大多数当前的治疗策略旨在通过不同的 RCD 途径在癌细胞中选择性地诱导细胞死亡。在这篇综述中，我们详细描述了五种 RCD 途径与肿瘤发生和癌症进展的关系。还提出了这些关键效应分子在肿瘤诊断和治疗反应中的一些潜在价值。然后，我们回顾并强调了基于小分子化合物、免疫检查点抑制剂和纳米颗粒诱导的 PANoptosis 和铁死亡在癌症治疗方面的最新进展。总之，这些发现可能为填补癌症发病机制和 RCD 途径之间的空白提供有意义的证据，以开发更好的癌症治疗策略。
