The role of metabolic reprogramming in liver cancer and its clinical perspectives

Primary liver cancer (PLC), which includes hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a leading cause of cancer-related death worldwide. Chronic liver diseases, such as hepatitis B and C infections and metabolic dysfunction-associated steatotic liver disease (...

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Main Authors: Mengxiao Lu, Yingjie Wu, MinMing Xia, Yixin Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2024.1454161/full
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author Mengxiao Lu
Yingjie Wu
MinMing Xia
Yixin Zhang
author_facet Mengxiao Lu
Yingjie Wu
MinMing Xia
Yixin Zhang
author_sort Mengxiao Lu
collection DOAJ
description Primary liver cancer (PLC), which includes hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a leading cause of cancer-related death worldwide. Chronic liver diseases, such as hepatitis B and C infections and metabolic dysfunction-associated steatotic liver disease (MASLD), are key risk factors for PLC. Metabolic reprogramming, a defining feature of cancer, enables liver cancer cells to adapt to the demands of rapid proliferation and the challenging tumor microenvironment (TME). This manuscript examines the pivotal role of metabolic reprogramming in PLC, with an emphasis on the alterations in glucose, lipid, and amino acid metabolism that drive tumor progression. The Warburg effect, marked by increased glycolysis, facilitates rapid energy production and biosynthesis of cellular components in HCC. Changes in lipid metabolism, including elevated de novo fatty acid synthesis and lipid oxidation, support membrane formation and energy storage essential for cancer cell survival. Amino acid metabolism, particularly glutamine utilization, supplies critical carbon and nitrogen for nucleotide synthesis and maintains redox homeostasis. These metabolic adaptations not only enhance tumor growth and invasion but also reshape the TME, promoting immune escape. Targeting these metabolic pathways presents promising therapeutic opportunities for PLC. This review underscores the interaction between metabolic reprogramming and tumor immunity, suggesting potential metabolic targets for innovative therapeutic strategies. A comprehensive understanding of PLC’s intricate metabolic landscape may lead to more effective treatments and better patient outcomes. Integrating metabolomics, genomics, and proteomics in future research will be vital for identifying precise therapeutic targets and advancing personalized therapies for liver cancer.
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spelling doaj-art-77c6c4daeb704f0b843f8d80a20f57da2024-11-14T05:10:22ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-11-011410.3389/fonc.2024.14541611454161The role of metabolic reprogramming in liver cancer and its clinical perspectivesMengxiao LuYingjie WuMinMing XiaYixin ZhangPrimary liver cancer (PLC), which includes hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a leading cause of cancer-related death worldwide. Chronic liver diseases, such as hepatitis B and C infections and metabolic dysfunction-associated steatotic liver disease (MASLD), are key risk factors for PLC. Metabolic reprogramming, a defining feature of cancer, enables liver cancer cells to adapt to the demands of rapid proliferation and the challenging tumor microenvironment (TME). This manuscript examines the pivotal role of metabolic reprogramming in PLC, with an emphasis on the alterations in glucose, lipid, and amino acid metabolism that drive tumor progression. The Warburg effect, marked by increased glycolysis, facilitates rapid energy production and biosynthesis of cellular components in HCC. Changes in lipid metabolism, including elevated de novo fatty acid synthesis and lipid oxidation, support membrane formation and energy storage essential for cancer cell survival. Amino acid metabolism, particularly glutamine utilization, supplies critical carbon and nitrogen for nucleotide synthesis and maintains redox homeostasis. These metabolic adaptations not only enhance tumor growth and invasion but also reshape the TME, promoting immune escape. Targeting these metabolic pathways presents promising therapeutic opportunities for PLC. This review underscores the interaction between metabolic reprogramming and tumor immunity, suggesting potential metabolic targets for innovative therapeutic strategies. A comprehensive understanding of PLC’s intricate metabolic landscape may lead to more effective treatments and better patient outcomes. Integrating metabolomics, genomics, and proteomics in future research will be vital for identifying precise therapeutic targets and advancing personalized therapies for liver cancer.https://www.frontiersin.org/articles/10.3389/fonc.2024.1454161/fullliver cancerhepatocellular carcinomametabolic dysfunction-associated steatotic liver diseasemetabolic reprogrammingWarburg effectlipid metabolism
spellingShingle Mengxiao Lu
Yingjie Wu
MinMing Xia
Yixin Zhang
The role of metabolic reprogramming in liver cancer and its clinical perspectives
Frontiers in Oncology
liver cancer
hepatocellular carcinoma
metabolic dysfunction-associated steatotic liver disease
metabolic reprogramming
Warburg effect
lipid metabolism
title The role of metabolic reprogramming in liver cancer and its clinical perspectives
title_full The role of metabolic reprogramming in liver cancer and its clinical perspectives
title_fullStr The role of metabolic reprogramming in liver cancer and its clinical perspectives
title_full_unstemmed The role of metabolic reprogramming in liver cancer and its clinical perspectives
title_short The role of metabolic reprogramming in liver cancer and its clinical perspectives
title_sort role of metabolic reprogramming in liver cancer and its clinical perspectives
topic liver cancer
hepatocellular carcinoma
metabolic dysfunction-associated steatotic liver disease
metabolic reprogramming
Warburg effect
lipid metabolism
url https://www.frontiersin.org/articles/10.3389/fonc.2024.1454161/full
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