Metabolic Rewiring and Stemness: A Critical Attribute of Pancreatic Cancer Progression.

Ayoola O Ogunleye, Rama Krishna Nimmakayala, Surinder K Batra, Moorthy P Ponnusamy

Journal: Stem cells (Dayton, Ohio) 2023;41(5):417-430

PMID: 36869789

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive diseases with a poor 5-year survival rate. PDAC cells rely on various metabolic pathways to fuel their unlimited proliferation and metastasis. Reprogramming glucose, fatty acid, amino acid, and nucleic acid metabolisms contributes to PDAC cell growth. Cancer stem cells are the primary cell types that play a critical role in the progression and aggressiveness of PDAC. Emerging studies indicate that the cancer stem cells in PDAC tumors are heterogeneous and show specific metabolic dependencies. In addition, understanding specific metabolic signatures and factors that regulate these metabolic alterations in the cancer stem cells of PDAC paves the way for developing novel therapeutic strategies targeting CSCs. In this review, we discuss the current understanding of PDAC metabolism by specifically exploring the metabolic dependencies of cancer stem cells. We also review the current knowledge of targeting these metabolic factors that regulate CSC maintenance and PDAC progression.

© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

Address: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.; Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
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