Background: Cellular metabolism plays a pivotal role in the development and progression of pancreatic ductal adenocarcinoma (PDAC), with dysregulated metabolic pathways contributing to tumorigenesis and therapeutic resistance. Distinct metabolic heterogeneity in pancreatic cancer significantly impacts patient prognosis, as variations in metabolic profiles influence tumor behavior and treatment responses. Scope of the Review: This review explores the intricate interplay between mitochondrial dynamics, mitophagy, and cellular metabolism in PDAC. We discuss the significance of mitophagy dysregulation in PDAC pathogenesis, emphasizing its influence on treatment responses and prognosis. Furthermore, we analyze the impact of mitochondrial dynamics alterations, including fission and fusion processes, on PDAC progression and tumorigenesis. Major Conclusion: Targeting mitochondrial metabolism holds promise for advancing PDAC therapeutics. Ongoing clinical trials underscore the therapeutic potential of modulating key regulators of mitochondrial dynamics and mitophagy. Despite inherent challenges, these approaches offer diverse strategies to enhance treatment efficacy and improve patient outcomes.

Metabolic plasticity in pancreatic cancer: The mitochondrial connection

Ghiglione, Noemi
First
;
Abbo, Damiano;Bushunova, Anastasia;Costamagna, Andrea;Porporato, Paolo Ettore;Martini, Miriam
Last
2024-01-01

Abstract

Background: Cellular metabolism plays a pivotal role in the development and progression of pancreatic ductal adenocarcinoma (PDAC), with dysregulated metabolic pathways contributing to tumorigenesis and therapeutic resistance. Distinct metabolic heterogeneity in pancreatic cancer significantly impacts patient prognosis, as variations in metabolic profiles influence tumor behavior and treatment responses. Scope of the Review: This review explores the intricate interplay between mitochondrial dynamics, mitophagy, and cellular metabolism in PDAC. We discuss the significance of mitophagy dysregulation in PDAC pathogenesis, emphasizing its influence on treatment responses and prognosis. Furthermore, we analyze the impact of mitochondrial dynamics alterations, including fission and fusion processes, on PDAC progression and tumorigenesis. Major Conclusion: Targeting mitochondrial metabolism holds promise for advancing PDAC therapeutics. Ongoing clinical trials underscore the therapeutic potential of modulating key regulators of mitochondrial dynamics and mitophagy. Despite inherent challenges, these approaches offer diverse strategies to enhance treatment efficacy and improve patient outcomes.
2024
92
Online ahead of print
Online ahead of print
https://www.sciencedirect.com/science/article/pii/S2212877824002205?via=ihub
Metabolism; Mitochondria; Mitophagy; Oxidative phosphorylation; Pancreatic cancer
Ghiglione, Noemi; Abbo, Damiano; Bushunova, Anastasia; Costamagna, Andrea; Porporato, Paolo Ettore; Martini, Miriam
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/2048951
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