e, DNA Therefore, epigenetic modifications are akin to rapid so

e., DNA. Therefore, epigenetic modifications are akin to rapid software updates that only involve alterations to gene expression or output rather than the

genetic sequence itself. In contrast to the permanence of DNA mutations, the reversibility of epigenetic aberrations find more constitutes an attractive therapeutic target. From an information technology perspective, it is possible to liken the tumor to malware designed specifically to damage or disrupt the source code of normal tissue through its pattern of gene expression. The DNA of tumor cells is to computer hardware as epigenetics is to system software. While the DNA hardware is fixed and unchangeable, epigenetics, like software, is a form of code, and code is “hackable” or modifiable. Hence with epigenetic agents, gene expression in tumors is reprogrammable in the same way that computer code can be rewritten. Just as malicious

code can be reengineered or neutralized, a feasible solution to the widespread problem of chemoresistance is to reprogram the tumor to restore sensitivity to previously tried therapies. Not surprisingly, this is perhaps easier said than done; however, it is becoming increasingly evident that chemoresistance is not necessarily written in stone; after all, the epigenome, by definition, Selleckchem GSK-3 inhibitor is editable, like any software [1], and while the parts of the epigenome that code for chemoresistance are unknown, clues about the “why and how” have emerged from

a commonality between the putative mechanisms of action of the agents described in this review. While epigenetics is an exploitable anticancer mechanism, the plasticity of epigenetic changes, with subsequent molecular alterations that regulate the neoplastic phenotype, contributes to carcinogenesis, tumor promotion, chemoresistance, and radioresistance as much as or more than genetic variability [2]. In particular, the yin of epigenetic silencing of tumor suppressor genes is an important mechanism for carcinogenesis. For example, MGMT hypermethylation, plays a direct role 2-hydroxyphytanoyl-CoA lyase in the accumulation of G-to-A mutations in the KRAS gene in colorectal tumors. This is the dark side of epigenetics: that it underlies and subserves the malignant phenotype. Conversely, since turnabout is fair play, the yang of epigenetic reactivation of these same silenced tumor suppressor genes is an invaluable anticancer strategy [3], [4], [5], [6], [7], [8] and [9]. Methyltransferases (MTases) transfer a methyl group to the C5 position of cytosine guanine dinucleotides (CpG). Overexpressed MTases lead to cytosine guanine dinucleotide hypermethylation around transcriptional start sites, which is associated with gene silencing and cancer [10]. MTases are an important player in many processes, and thus, their inhibition disrupts multiple signaling pathway nodes [11].

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