Metabolic reprogramming and its clinical implication for liver cancer.

Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 8302946 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-3350 (Electronic) Linking ISSN: 02709139 NLM ISO Abbreviation: Hepatology Subsets: MEDLINE

Publication: 2023- : [Philadelphia] : Wolters Kluwer Health, Inc.
Original Publication: Baltimore, MD : Williams & Wilkins, [c1981]-

Liver Neoplasms*/metabolism ; Carcinoma, Hepatocellular*/pathology ; Non-alcoholic Fatty Liver Disease* ; Bile Duct Neoplasms*/pathology; Humans ; Bile Ducts, Intrahepatic/pathology

Cancer cells often encounter hypoxic and hypo-nutrient conditions, which force them to make adaptive changes to meet their high demands for energy and various biomaterials for biomass synthesis. As a result, enhanced catabolism (breakdown of macromolecules for energy production) and anabolism (macromolecule synthesis from bio-precursors) are induced in cancer. This phenomenon is called "metabolic reprogramming," a cancer hallmark contributing to cancer development, metastasis, and drug resistance. HCC and cholangiocarcinoma (CCA) are 2 different liver cancers with high intertumoral heterogeneity in terms of etiologies, mutational landscapes, transcriptomes, and histological representations. In agreement, metabolism in HCC or CCA is remarkably heterogeneous, although changes in the glycolytic pathways and an increase in the generation of lactate (the Warburg effect) have been frequently detected in those tumors. For example, HCC tumors with activated β-catenin are addicted to fatty acid catabolism, whereas HCC tumors derived from fatty liver avoid using fatty acids. In this review, we describe common metabolic alterations in HCC and CCA as well as metabolic features unique for their subsets. We discuss metabolism of NAFLD as well, because NAFLD will likely become a leading etiology of liver cancer in the coming years due to the obesity epidemic in the Western world. Furthermore, we outline the clinical implication of liver cancer metabolism and highlight the computation and systems biology approaches, such as genome-wide metabolic models, as a valuable tool allowing us to identify therapeutic targets and develop personalized treatments for liver cancer patients.
(Copyright © 2023 American Association for the Study of Liver Diseases.)

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P50 CA210964 United States CA NCI NIH HHS; R01 CA160069 United States CA NCI NIH HHS

Date Created: 20230110 Date Completed: 20231023 Latest Revision: 20240617

20240617

PMC10315435

10.1097/HEP.0000000000000005

36626639