Chemoprevention of Hepatocellular Carcinoma with Retinoid

Abstract

In the general classification of cancer prevention, chemoprevention is defined as an intervention to prevent carcinogenesis by the reverse or the arrest of transformed clones using a physiological mechanism. The reverse of such clones is done by differentiation induction, and the arrest is mainly achieved by apoptosis induction. The concept of chemoprevention, thus, requires that the target organ essentially contains premalignant or latent malignant clones. In this assumption, premalignant clones respond to the transformed cells on the promotion or conversion phase of multistep carcinogenesis, and latent malignant clones indicate the cells on the progression phase. The latter clone is regarded to have already completed the genomic and molecular process of carcinogenesis, but can not yet be detected using common diagnostic modalities such as medical imagings and serum tumor markers. Successful chemoprevention is performed by deletion of these clones and, thus, is also called clonal deletion. In the case of liver cancer, those transformed clones are supposed to exist in cirrhotic liver including remnant liver after surgical resection or ablation therapy of initial HCC.

Recent advances in the studies on cancer chemoprevention revealed that the most promising molecular target is nuclear steroid hormone receptor super-family proteins. These receptors include ER, TR, RAR, RXR, PPAR, VDR and others, and regulate cellular differentiation and programmed cell death as ligand-dependent transcription factors. In hepatitis virus-related liver carcinogenesis, the role of RXR and RAR seems to be important from recent experimental analyses. In particular, malfunction of RXR is the most recent topic in the mechanism of liver carcinogenesis (Cancer Res 2001, Hepatology 2002).