Aberrant DNA methylation and histone deacetylation participate in cancer development and progression;
Until short time ago we considered cancer as the result of genetic mutations, but recent studies have shown that genetic mutations are not the only responsible for tumorigenesis. Although the genome contains all the information needed to encode the entire set of proteins, the expression of this information is regulated by the epigenome. Hypermethylation is one of the best known epigenetic events in mammalian cells. Over the last few years, many studies have found that other epigenetic events, such as deacetylation and methylation of histones, are involved in the complex mechanism that regulates promoter transcription. Hence, their reversal by inhibitors of DNA methylation and histone deacetylases is a promising cancer therapy.
The drugs that target histone deacetylases (HDACs) are called epigenetic drugs or histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) in hibitors Their target is chromatin unspecifically, and they may act upon most or all tumor types. In the last years, valproic acid (VPA) emerged as a promising drug for cancer treatment. VPA has shown potent antitumor effects in either alone or in combination with molecular targeted drugs and cytotoxic drugs. Despite in general, industry is not particularly interested in funding the clinical development of VPA, existing preclinical and preliminary clinical data strongly suggest that VPA could be a drug that eventually will be used in combination therapies, either with classical cytotoxic drugs, other molecular-targeted drugs or radiation in a number of solid tumors.
In treatment of colorectal cancer, the combination of thalidomide, celecoxib, valproic acid with low dose irinotecan is very effective.
In Japan, the clinical trial of thalidomide, celecoxib with cytotoxic drug is prohibited by the ignorance of Kazuhiko Nishi ( 西和彦 ), Bureaucracy of the Ministry of Health, Labor and Welfare.