Wang Shaohui, Guo Sa, Guo Jing, Du Qinyun, Wu Cen, Wu Yeke, Zhang Yi
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine Chengdu University of Traditional Chinese Medicine Chengdu China.
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu China.
MedComm (2020). 2024 Sep 4;5(9):e693. doi: 10.1002/mco2.693. eCollection 2024 Sep.
Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell death can provide novel therapeutic strategies for battling cancer. This review explores several key cell death mechanisms of apoptosis, necroptosis, autophagic cell death, ferroptosis, and pyroptosis. The research gap addressed involves a thorough analysis of how these cell death pathways can be precisely targeted for cancer therapy, considering tumor heterogeneity and adaptation. It delves into genetic and epigenetic factors and signaling cascades like the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways, which are critical for the regulation of cell death. Additionally, the interaction of the microenvironment with tumor cells, and particularly the influence of hypoxia, nutrient deprivation, and immune cellular interactions, are explored. Emphasizing therapeutic strategies, this review highlights emerging modulators and inducers such as B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), chloroquine, and innovative approaches to induce ferroptosis and pyroptosis. This review provides insights into cancer therapy's future direction, focusing on multifaceted approaches to influence cell death pathways and circumvent drug resistance. This examination of evolving strategies underlines the considerable clinical potential and the continuous necessity for in-depth exploration within this scientific domain.
细胞死亡调控对于组织稳态至关重要，其失调往往是癌症发展的基础。了解细胞死亡的不同途径可为对抗癌症提供新的治疗策略。本综述探讨了凋亡、坏死性凋亡、自噬性细胞死亡、铁死亡和焦亡等几种关键的细胞死亡机制。所解决的研究空白涉及全面分析如何针对肿瘤异质性和适应性，精确地将这些细胞死亡途径作为癌症治疗的靶点。它深入研究了遗传和表观遗传因素以及信号级联反应，如磷脂酰肌醇3激酶/蛋白激酶B/雷帕霉素哺乳动物靶蛋白（PI3K/AKT/mTOR）和丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）途径，这些对细胞死亡的调控至关重要。此外，还探讨了微环境与肿瘤细胞的相互作用，特别是缺氧、营养剥夺和免疫细胞相互作用的影响。本综述强调治疗策略，重点介绍了新兴的调节剂和诱导剂，如B细胞淋巴瘤2（BCL2）同源结构域3（BH3）模拟物、肿瘤坏死因子相关凋亡诱导配体（TRAIL）、氯喹，以及诱导铁死亡和焦亡的创新方法。本综述提供了癌症治疗未来方向的见解，重点是影响细胞死亡途径和规避耐药性的多方面方法。对不断发展的策略的审视强调了巨大的临床潜力以及在这一科学领域进行深入探索的持续必要性。
