Yonsei Med J.  2018 Dec;59(10):1143-1149. 10.3349/ymj.2018.59.10.1143.

Cancer Metabolism as a Mechanism of Treatment Resistance and Potential Therapeutic Target in Hepatocellular Carcinoma

• Lee M
• Ko H
• Yun M

• KMID: 2426327
• DOI: http://doi.org/10.3349/ymj.2018.59.10.1143

Abstract

Various molecular targeted therapies and diagnostic modalities have been developed for the treatment of hepatocellular carcinoma (HCC); however, HCC still remains a difficult malignancy to cure. Recently, the focus has shifted to cancer metabolism for the diagnosis and treatment of various cancers, including HCC. In addition to conventional diagnostics, the measurement of enhanced tumor cell metabolism using F-18 fluorodeoxyglucose (18F-FDG) for increased glycolysis or C-11 acetate for fatty acid synthesis by positron emission tomography/computed tomography (PET/CT) is well established for clinical management of HCC. Unlike tumors displaying the Warburg effect, HCCs vary substantially in terms of 18F-FDG uptake, which considerably reduces the sensitivity for tumor detection. Accordingly, C-11 acetate has been proposed as a complementary radiotracer for detecting tumors that are not identified by 18F-FDG. In addition to HCC diagnosis, since the degree of 18F-FDG uptake converted to standardized uptake value (SUV) correlates well with tumor aggressiveness, 18F-FDG PET/CT scans can predict patient outcomes such as treatment response and survival with an inverse relationship between SUV and survival. The loss of tumor suppressor genes or activation of oncogenes plays an important role in promoting HCC development, and might be involved in the "metabolic reprogramming" of cancer cells. Mutations in various genes such as TERT, CTNNB1, TP53, and Axin1 are responsible for the development of HCC. Some microRNAs (miRNAs) involved in cancer metabolism are deregulated in HCC, indicating that the modulation of genes/miRNAs might affect HCC growth or metastasis. In this review, we will discuss cancer metabolism as a mechanism for treatment resistance, as well as an attractive potential therapeutic target in HCC.

Keyword

Hepatocellular carcinoma; cancer metabolism; positron emission tomography/computed tomography (PET/CT); drug resistance

MeSH Terms

Carcinoma, Hepatocellular*
Diagnosis
Drug Resistance
Electrons
Fluorodeoxyglucose F18
Genes, Tumor Suppressor
Glycolysis
Humans
Metabolism*
MicroRNAs
Molecular Targeted Therapy
Neoplasm Metastasis
Oncogenes
Positron-Emission Tomography and Computed Tomography
Fluorodeoxyglucose F18
MicroRNAs

Figure

• 

  Fig. 1 Hepatocellular carcinoma positive for F-18 fluorodeoxyglucose (A), but negative for C-11 acetate (B).

• 

  Fig. 2 Hepatocellular carcinoma negative for F-18 fluorodeoxyglucose (A), but positive C-11 acetate (B).

• 

  Fig. 3 Differences in the expression of glucose transport 1 (A and C) and monocarboxylate transporter 1 (B and D) in hepatocellular carcinoma (HCC) samples, based on 18F-fluorodeoxyglucose and 11C-acetate uptake. Human HCC samples were used. Immunohistochemistry (IHC) was performed as described previously.16 After antigen retrieval, IHC was performed using indicated antibodies. Scale bars: 40 µm.

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