DNA Demethylating Agents and Epigenetic Therapy of Cancer

• Published in: Advances in Genetics Vol. 70; pp. 327 - 340
• Main Authors: Mani, Samson, Herceg, Zdenko
• Format: Book Chapter Journal Article
• Language: English
• Published: United States Elsevier Science & Technology 2010
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; DNA Methylation - drug effects; Epigenesis, Genetic; Genes, Tumor Suppressor; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylase Inhibitors - therapeutic use; Histones - metabolism; Humans; Mice; Mice, Knockout; MicroRNAs; Neoplasms - drug therapy; Neoplasms - genetics; RNA Interference
• ISBN: 0123808669; 9780123808660
• ISSN: 0065-2660
• DOI: 10.1016/B978-0-12-380866-0.60012-5

Epigenetic events have been associated with virtually every step of tumor development and progression, and epigenetic alterations are believed to occur early in tumor development and may precede the malignant process. In contrast to genetic changes, epigenetic alterations arise in a gradual manner, leading to a progressive silencing of specific genes. An important distinction between epigenetic and genetic alterations is intrinsic reversibility of the former, making cancer-associated changes in DNA methylation, histone modifications, and expression of noncoding RNAs attractive targets for therapeutic intervention. This realization has triggered an impressive quest for the development of “epigenetic drugs” and epigenetic therapies. A number of agents have been subjected to an intensive investigation, many of which have been found capable of altering epigenetic states, including DNA methylation patterns and histone modification states. Many of these agents are currently being tested in clinical trials, while several of them are already used in clinics. This review will focus on the recent advances in the development of epigenetic drugs based on the inhibition of DNA methylation. Combinatorial therapies that couple DNA demethylating agents with histone deacetylase inhibitors will also be discussed.