User:Leanafigueroa/Demethylating agent

Clinical Applications
The silencing of genes created by abnormal DNA methylation is a major contributor to the formation of cancerous tumors. Variations in DNA methylation of normal cells compared to malignant cells shows a prominent mechanism in how cancerous cells proliferate. Those variations are particularly prevalent in cell cycle regulation, DNA repair, and natural tumor suppression mechanisms. A leading therapeutic strategy in treating solid tumors stems from the use of demethylating agents to suppress DNA methylation in cancerous growths. Azacitidine and decitabine are both frequently used demethylating agents while decitabine is significantly more potent in its demethylating abilities. Both of these drugs are inhibitors of DNA Methyltransferases (DNMT) which are enzymes that are responsible for methylating DNA. In the 1970’s, these drugs have shown promising results in hematological cancers in organisms such as mice. The FDA initially rejected the use of azacitidine clinically due to negative side effects caused by elevated toxicity levels. In later clinical trials performed on patients with MDS, myelodysplastic syndromes, azacitidine provided effective and exhibited consistent results which led to FDA approval in 2004. The commercial name of azacitidine became Vidaza. Decitabine, with the commercial name Dacogen, followed with FDA approval in 2006. As more research is completed in the field of genetic mutations, specifically involving DNA Methylation, these drugs can be utilized to their maximum efficiency to clinically treat cancerous tumors. As of 2017, there were no approved demethylating agents for the treatment of solid tumors which can be a focus of research in the future. Treatment utilizing demethylating agents can have further clinical use by targeting cancer stem cells and triggering apoptosis.