Therapeutic implications of DNA methylation.
Cancer growth and metastasis requires reprogramming of the expression of multiple genes. The epigenome, which is comprised of chromatin and the patterns of DNA methylation, sets up and maintains gene expression programs. As expected from the broad changes in gene expression in cancer, which are characterized by both silencing and activation of multiple genes, the epigenome of cancer cells is distinguished by aberration of DNA methylation patterns, which include both hypo- and hypermethylation and aberrant regulation of DNA methylation enzymes. In contrast to genetic alterations, which are fixed and are not amenable to therapeutic intervention, pharmacological agents could alter DNA methylation patterns. This raises the prospect that DNA methylation-targeted drugs will reverse cancer growth and metastasis. One of the main challenges however, is to understand the relative role of hypo- and hypermethylation in order to achieve a balance of epigenetic therapeutic agents with positive outcome and reduced adverse effects.
Szyf
Moshe
M
Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, PQ H3G 1Y6, Canada. moshe.szyf@mcgill.ca
D000818:Animals; D002843:Chromatin / Q000737:chemistry; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000502:physiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D012436:S-Adenosylmethionine / Q000627:therapeutic use
D002843:Chromatin; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C489325:MBD2 protein, human; D012436:S-Adenosylmethionine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases