Chemoprevention of hepatocellular carcinoma by acyclic retinoid

Front Biosci (Landmark Ed). 2011 Jan 1;16:759-69. doi: 10.2741/3718.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / prevention & control*
  • Chemoprevention
  • Clinical Trials as Topic
  • Clonal Deletion
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / prevention & control*
  • Receptors, Retinoic Acid / drug effects
  • Receptors, Retinoic Acid / physiology
  • Retinoid X Receptors / drug effects
  • Retinoid X Receptors / physiology
  • Tretinoin / analogs & derivatives*
  • Tretinoin / pharmacology
  • Tretinoin / therapeutic use

Substances

  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Tretinoin
  • 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid