Potential Epigenetic Modifiers Targeting the Alteration of Methylation in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is one of the most frequent causes of cancer-related death worldwide. Chemotherapeutic agents used in CRC treatment include oxaliplatin, irinotecan, leucovorin, Tegafur-Uracil, capecitabine, 5-fluorouracil, and monoclonal antibodies. The development of other effective drugs is urgently needed for CRC patients. As the epigenetics of CRC is increasingly understood, epigenetic modifiers (or epidrugs) targeting epigenetic mechanisms could play an important role in this process. During the past two decades, many studies have demonstrated that many specific genes are silenced by hypermethylation of their promoters in CRC, which means that the expression of these genes could be restored since epigenetic alterations are reversible. In fact, some molecules have been studied for their ability to inhibit DNA methyltransferases, and the results showed that silenced genes were reactivated. These molecules could be natural, such as curcumin, tea polyphenols, quercetin, and nanaomycycin A, or synthetic, such as 5-azacytidine, decitabine, procainamide, and zebularine. On the other hand, we hypothesized in this article that ten-eleven translocation inhibitors could be another class of epigenetic modifiers since they could prevent chromosomal instability through decreasing the global hypomethylation of genomic DNA. Some studies have reported that some ten-eleven translocation inhibitors exhibit anticancer effects, which supports our hypothesis. Additionally, we have proposed combinations of these epigenetic modifiers according to different parameters.