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Glucometabolic reprogramming: From trigger to therapeutic target in hepatocellular carcinoma

Journal

FRONTIERS IN ONCOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.953668

Keywords

hepatocellular carcinoma; glucometabolic reprogramming; tumor microenvironment; drug resistance; antitumor agents; environmental stress

Categories

Funding

  1. Hong Kong Scholars Program [XJ2020012]
  2. National Natural Science Foundation of China [81902431]
  3. Special Project of China Postdoctoral Science Foundation [2019T120279]
  4. China Postdoctoral Science Foundation [2018M641849, 2018M640311]
  5. Postgraduate Innovative Research Project of Harbin Medical University [YJSCX2016-21HYD]
  6. Foundation of Key Laboratory of Myocardial Ischemia, Ministry of Education [KF201810]
  7. Chen Xiaoping Foundation for the Development of Science and Technology of Hubei Province [CXPJJH11800004-001, CXPJJH11800004-003]

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Glucometabolic reprogramming plays a significant role in the development and treatment of hepatocellular carcinoma (HCC). By altering the glucose metabolism pathway, HCC cells can survive and thrive in nutrient-poor tumor microenvironments and evade immune surveillance. Targeted interventions against glucose metabolism and signaling pathways hold promising prospects for HCC therapy.
Glucose, the central macronutrient, releases energy as ATP through carbon bond oxidation and supports various physiological functions of living organisms. Hepatocarcinogenesis relies on the bioenergetic advantage conferred by glucometabolic reprogramming. The exploitation of reformed metabolism induces a uniquely inert environment conducive to survival and renders the hepatocellular carcinoma (HCC) cells the extraordinary ability to thrive even in the nutrient-poor tumor microenvironment. The rewired metabolism also confers a defensive barrier which protects the HCC cells from environmental stress and immune surveillance. Additionally, targeted interventions against key players of HCC metabolic and signaling pathways provide promising prospects for tumor therapy. The active search for novel drugs based on innovative mutation targets is warranted in the future for effectively treating advanced HCC and the preoperative downstage. This article aims to review the regulatory mechanisms and therapeutic value of glucometabolic reprogramming on the disease progression of HCC, to gain insights into basic and clinical research.

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