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Cell death in pancreatic cancer: from pathogenesis to therapy
Nature Reviews Gastroenterology & Hepatology ( IF 65.1 ) Pub Date : 2021-07-30 , DOI: 10.1038/s41575-021-00486-6
Xin Chen 1, 2, 3 , Herbert J Zeh 3 , Rui Kang 3 , Guido Kroemer 4, 5, 6, 7, 8 , Daolin Tang 1, 3
Affiliation  

Pancreatic cancer is a devastating gastrointestinal cancer characterized by late diagnosis, limited treatment success and dismal prognosis. Exocrine tumours account for 95% of pancreatic cancers and the most common pathological type is pancreatic ductal adenocarcinoma (PDAC). The occurrence and progression of PDAC involve multiple factors, including internal genetic alterations and external inflammatory stimuli. The biology and therapeutic response of PDAC are further shaped by various forms of regulated cell death, such as apoptosis, necroptosis, ferroptosis, pyroptosis and alkaliptosis. Cell death induced by local or systemic treatments suppresses tumour proliferation, invasion and metastasis. However, unrestricted cell death or tissue damage might result in an inflammation-related immunosuppressive microenvironment, which is conducive to tumour progression or recurrence. The precise extent to which cell death affects PDAC is not yet well described. A growing body of preclinical and clinical studies document significant correlations between mutations (for example, in KRAS and TP53), stress responses (such as hypoxia and autophagy), metabolic reprogramming and chemotherapeutic responses. Here, we describe the molecular machinery of cell death, discuss the complexity and multifaceted nature of lethal signalling in PDAC cells, and highlight the challenges and opportunities for activating cell death pathways through precision oncology treatments.



中文翻译:

胰腺癌的细胞死亡:从发病机制到治疗

胰腺癌是一种破坏性的胃肠道癌症,其特点是诊断晚、治疗成功率有限和预后不良。外分泌肿瘤占胰腺癌的 95%,最常见的病理类型是胰腺导管腺癌 (PDAC)。PDAC的发生和发展涉及多种因素,包括内部基因改变和外部炎症刺激。PDAC 的生物学和治疗反应进一步受到各种形式的调节细胞死亡的影响,例如细胞凋亡、坏死性凋亡、铁死亡、细胞焦亡和碱性细胞死亡。局部或全身治疗诱导的细胞死亡抑制肿瘤增殖、侵袭和转移。然而,不受限制的细胞死亡或组织损伤可能会导致炎症相关的免疫抑制微环境,有利于肿瘤的进展或复发。细胞死亡影响 PDAC 的确切程度尚未得到很好的描述。越来越多的临床前和临床研究记录了突变之间的显着相关性(例如,在KRASTP53)、应激反应(如缺氧和自噬)、代谢重编程和化疗反应。在这里,我们描述了细胞死亡的分子机制,讨论了 PDAC 细胞中致死信号的复杂性和多面性,并强调了通过精准肿瘤治疗激活细胞死亡途径的挑战和机遇。

更新日期:2021-08-01
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