Characterization of metabolic landscape in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, accounting for approximately 75%-85% of primary liver cancers. Metabolic alterations have been labeled as an emerging hallmark of tumors. Specially, the last decades have registered a significant improvement in our understanding of the role of metabolism in driving the carcinogenesis and progression of HCC. In this paper, we provide a review of recent studies that investigated the metabolic traits of HCC with a specific focus on three common metabolic alterations involving glycolysis, lipid metabolism, and glutamine addiction which have been gaining much attention in the field of HCC. Next, we describe some representative diagnostic markers or tools, and promising treatment agents that are proposed on the basis of the aforementioned metabolic alterations for HCC. Finally, we present some challenges and directions that may promisingly speed up the process of developing objective diagnostic markers and therapeutic options underlying HCC. Specifically, we recommend future investigations to carefully take into account the influence of heterogeneity, control for study-specific confounds, and invite the validation of existing biomarkers.

WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities

“…Other aspects of metabolic reprograming in HCC, mostly unrelated to CTNBB1 mutations and enhanced β-catenin activity have been reviewed elsewhere. 191 , 192 , 193 , 194 …”

Metabolic Heterogeneity, Plasticity, and Adaptation to “Glutamine Addiction” in Cancer Cells: The Role of Glutaminase and the GTωA [Glutamine Transaminase—ω-Amidase (Glutaminase II)] Pathway

“…Many articles have been published (e.g., [ 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 ]) that discuss the canonical pathway for l -glutamine conversion to α-ketoglutarate in glutamine addiction (i.e., l -glutamine → l -glutamate ⇆ α-ketoglutarate) in cancer cells. However, due mostly to reasons provided in Section 10.2 .…”

“…It is anticipated that the availability of pure KGM product will prompt greater attention to the study of L-glutamine transaminases in health and disease and assist in the detailed study of the ω-amidase-catalyzed conversion of KGM to α-ketoglutarate and ammonium [149]. Many articles have been published (e.g., [150][151][152][153][154][155][156][157]) that discuss the canonical pathway for L-glutamine conversion to α-ketoglutarate in glutamine addiction (i.e., L-glutamine → Lglutamate α-ketoglutarate) in cancer cells. However, due mostly to reasons provided in Section 10.2. above, only perfunctory attention has been accorded the GTωA pathway (i.e., L-glutamine KGM → α-ketoglutarate).…”

Exploring the therapeutic and anti-tumor properties of morusin: a review of recent advances

“…Synchronic carcinogenesis is the phenomenon of development of multiple tumors simultaneously which is a common factor in HCC ( Gisder et al, 2022 ). Although chemotherapy, radiation, immunotherapy, and surgery have long been used to treat HCCs, antiglycolytic drugs like 3-bromopyruvate may also be utilized alone or in combination with other traditional anticancer drugs like sorafenib ( Wu et al, 2021a ). Additionally, AMPK, PI3K/Akt pathway, HIF-1, and c-Myc have been identified as proteins associated with aerobic glycolysis in hepatocellular cancer.…”