Cell death in pancreatic cancer: from pathogenesis to therapy.

Abstract

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.

• Authors: Xin Chen, Herbert J Zeh, Rui Kang, Guido Kroemer, Daolin Tang
• Journal: Nature reviews. Gastroenterology & hepatology (Nat Rev Gastroenterol Hepatol) Vol. 18 Issue 11 Pg. 804-823 (11 2021) ISSN: 1759-5053 [Electronic] England
• PMID: 34331036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2021. Springer Nature Limited.

Chemical References

• KRAS protein, human
• TP53 protein, human
• Tumor Suppressor Protein p53
• Proto-Oncogene Proteins p21(ras)

Topics

• Apoptosis (physiology)
• Autophagy (physiology)
• Carcinoma, Pancreatic Ductal (drug therapy, metabolism, pathology)
• Cell Death (physiology)
• Cell Proliferation (physiology)
• Ferroptosis (physiology)
• Humans
• Hypoxia (metabolism)
• Necroptosis (physiology)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Pancreatic Neoplasms (drug therapy, metabolism, pathology)
• Proto-Oncogene Proteins p21(ras) (genetics)
• Pyroptosis (physiology)
• Tumor Suppressor Protein p53 (genetics)