Cell death in pancreatic cancer: from pathogenesis to therapy

Xin Chen, Herbert J. Zeh, Rui Kang, Guido Kroemer, Daolin Tang

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)804-823
Number of pages20
JournalNature Reviews Gastroenterology and Hepatology
Volume18
Issue number11
DOIs
StatePublished - Nov 2021

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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