Epigenetic Therapeutics: A New Weapon in the War Against Cancer

Abstract

The past 15 years have seen an explosion of discoveries related to the cellular regulation of phenotypes through epigenetic mechanisms. This regulation provides a software that packages DNA, without changing the primary base sequence, to establish heritable patterns of gene expression. In cancer, many aspects of the epigenome, controlled by DNA methylation, chromatin, and nucleosome positioning, are altered as one means by which tumor cells maintain abnormal states of self-renewal at the expense of normal maturation. Epigenetic and genetic abnormalities thus collaborate in cancer initiation and progression, as exemplified by frequent mutations in genes encoding proteins that control the epigenome. There is growing emphasis on using epigenetic therapies to reprogram neoplastic cells toward a normal state. Many agents targeting epigenetic regulation are under development and entering clinical trials. This review highlights the promise that epigenetic therapy, often in combination with other therapies, will become a potent tool for cancer management over the next decade.

Sexual dimorphism in cancer

“…This is especially true for steroid hormones 168,169 . Along these lines, a topic of great interest and translational potential is that of the interplay between their influence and epigenetic reprogramming of cells, with a well known interplay between ER and AR function and key histone and DNA modifying enzymes 13 , which can be targeted by a large battery of natural and synthetic compounds 170 .…”

Mutant ATRX: uncovering a new therapeutic target for glioma

“…Over the last few years, there have been advances in the development of therapies aiming to compensate for the epigenetic dysregulation present in cancer cells [120]. Although the epigenetic landscape in ATRX mutant cells has not been elucidated and varies according with the mutational signatures of the cell, the current evidence suggests that ATRX is mainly implicated in the chromatin silencing processes.…”

Differential DNA damaging effects of genotoxic agents from chewing tobacco and gutka

“…In spite of very low genotoxic effects of gutka components should be inferred that gutka may not initiate carcinogenesis, rather this observation suggests that chemical compositions within gutka may contribute towards oral carcinogenesis via epigenetic and deregulation of molecular signaling pathways. This finding may have implications in the existing views to suggest the role of genetic alterations by genotoxic agents, molecular signaling deregulations and epigenetic pathways in different type cancer development including oral cancer [8][9][10].…”