Open Access
Chemoprevention of hepatocellular carcinoma by acyclic retinoid
Masahito Shimizu1,Hiroyasu Sakai1,Hisataka Moriwaki1
Department of Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
DOI: 10.2741/3718 Volume 16 Issue 2, pp.759-769
Published: 01 January 2011
(This article belongs to the Special Issue Novel strategies for detection, prevention and treatment of cancer)

The prognosis for patients with hepatocellular carcinoma (HCC) is poor and effective prevention strategies are urgently required. Here, we review abnormalities in the expression and function of retinoids and their receptors, and how they play a critical role in the development of HCC. In particular, a malfunction of RXRalpha due to phosphorylation by Ras-MAPK signaling pathway is profoundly associated with liver carcinogenesis and thus may be a promising target for HCC chemoprevention. Acyclic retinoid (ACR), a synthetic retinoid, inhibits Ras-MAPK activation and RXRalpha phosphorylation, thereby suppressing growth in HCC-derived cells. In clinical trials, ACR has been shown to improve patient survival by preventing viral HCC development, a possible manifestation of the concept of "clonal deletion" therapy. "Combination chemoprevention" with ACR as the key drug has great potential to become an effective strategy for the prevention of liver carcinogenesis. In summary, both basic and clinical research strongly suggest that ACR plays a critical role in preventing the development of HCC and that "clonal deletion" therapy is one of the most practical approaches for this purpose.

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Masahito Shimizu, Hiroyasu Sakai, Hisataka Moriwaki. Chemoprevention of hepatocellular carcinoma by acyclic retinoid. Frontiers in Bioscience-Landmark. 2011. 16(2); 759-769.