Recent progress in molecular genetics has facilitated understanding of the mechanisms of
carcinogenesis. However, there is not yet any effective
therapy or prevention for
cancer based on the molecular mechanisms of
carcinogenesis. So-called "gene therapy" for
cancer is expected to become a new method of treatment, but there are still several serious problems with gene therapy. As a matter of fact, it seems impossible to adopt gene therapy for prevention. We therefore tried to develop a different method of
cancer prevention or
therapy based on the molecular mechanisms of
carcinogenesis. For instance, the tumor-suppressor gene p53 is mutated in about 50% of human
malignancies. It is known that p53 stimulates the promoter activities of p21/WAF1, gadd45 and bax genes, resulting in cell cycle arrest, DNA repair and apoptosis, respectively. Therefore, chemical compounds that can stimulate these genes should compensate for the function of p53. As a model of this, we found that
histone deacetylase inhibitors such as
butyrate or
trichostatin A dramatically stimulate the p21/WAF1 gene promoter through the Spl sites, resulting in cell cycle arrest. Interestingly, another group has recently reported that phenylbutyrate, which is also known as a
histone deacetylase inhibitor, is very effective for
leukemia patients. We therefore consider methods of up-regulating p21/WAF, gadd45 or bax genes should be useful for
cancer therapy and termed this method "Gene-regulating
chemotherapy". Theoretically, the chemicals up-regulating such genes should be also useful for
chemoprevention, and we also termed it as "Gene-regulating
chemoprevention". In conclusion, we propose that "Gene-regulating
chemotherapy or
chemoprevention" may be a promising new method for
cancer therapy or prevention and
histone deacetylase inhibitor is a good candidate for this method.