Warburg Effect and Type II Glucose Transporter Inhibitors as a Potential Targeted Therapy for Liver Cancer: A Review
DOI:
https://doi.org/10.48048/tis.2024.8309Keywords:
GLUT-2 inhibitor, Glucose transporters, Targeted therapy, Liver cancer, Small molecule synthesisAbstract
Cancer cells demonstrate enhanced survival owing to the underlying metabolic changes that accelerate tumor growth. Hepatocellular carcinoma (HCC) cells exhibit the Warburg effect, a hallmark of cancer metabolism associated with aberrant proliferation. This review critically assesses the existing obstacles in developing selective type II glucose transporter GLUT-2 inhibitors, examining the inhibition of GLUT-2 by natural extracts and synthesized compounds. Liver cells regulate glucose uptake and release via GLUT-2. Dysregulated GLUT-2 expression in HCC increases glucose absorption and metabolism, thereby fueling tumor growth. Targeting inhibition of GLUT-2 may delay tumor development and improve therapeutic sensitivity by preventing glucose uptake by cancer cells. Natural and synthetic chemicals that specifically limit GLUT-2 activity are promising GLUT-2 inhibitors. GLUT-2 inhibitors must be engineered with precision to specifically target GLUT-2 while avoiding interference with other GLUT functions. Targeted therapy is complicated by difficulties in determining the mechanisms underlying GLUT-2 dysregulation in various malignancies. New HCC treatments require a deep understanding of GLUT-2 and cancer metabolism as well as advances in pharmacological research and development. Conclusively, the targeting of GLUT-2 is a novel therapeutic strategy for HCC. Understanding the intricate role of GLUT-2 in the pathophysiology of HCC may lead to the development of tailored therapies for patients with HCC.
HIGHLIGHTS
- The Warburg effect, which emphasizes upregulated glucose metabolism in cancer cells, is a potential therapeutic target for liver cancer
- Class I glucose transporters are more expressed in liver cancer cells than in normal cells
- The Warburg effect is crucial for cancer cell metabolism and is related to cancer hallmarks such as cell proliferation, metastasis, and invasion
- Compounds that specifically inhibit glucose transporter type II can impair the energy production pathway critical for hepatocellular carcinoma cell survival
GRAPHICAL ABSTRACT
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