N-4- (carboxyphenyl) retinamide (RE) is a new drug developed by the Institute of Materia Medica, Chinese Academy of Medical Sciences. The cancer chemopreventive action of R Ⅱ is reviewed in this paper. The multicenter clinical trials indicated that R Ⅱ was effective against premalignancies such as oral leukoplakia, vulvar leukoplakia, dysplasia of the uterine cervix and stomach. Preclinical studies demonstrated that R Ⅱ was a potent anti-mutagenic and anti-promotion agent. It has significant protective effects on chromosome aberration, and can inhibit ornithine decarboxyase (ODC) activity induced by 12-0-tetradecanoylphorbol-3-ac-etate (TPA) and decreases protein kinase C (PKC) activity. In a panel of experimental models including DM-BA induced buccal pouch carcinogenesis in hamster, DMBA and croton oil-induced skin papilloma, ni-trososamine induced forestomach carcinogenesis in mice, and N-butyl-N- ( 4-hydroxybutyl) -nitrosamine (BBN) induced bladder carcinogenesis in rats, it was demonstrated that R Ⅱ was a potent anti-carcinogenic a-gent. Electron microscopic studies and cell cycle kinetic analysis revealed that R Ⅱ could decrease malignant degree of tumor cells in terms of cell morphology and growth characteristics, and tumor cells differentiation. Action mechanisms studies indicated that R Ⅱ inhibited the expression of oncogene c-myc and enhanced the expression of c-fos.

In summary, R Ⅱ is a promising chemopreventive agent in terms of its anticarcinogenesis activity and clinical efficacy for the treatment of oral leukoplakia and vulvar leukoplakia.