Switching on Epigenetic Therapy

Abstract

Reversible epigenetic changes that alter gene expression are a characteristic of many cancers and other diseases. Biotech companies are taking note and are starting to develop new drugs to reverse such pathogenic "epimutations."

Epigenetic Mechanisms in Inflammation

“…Progress in studies of epigenetic alterations during inflammatory response opens opportunities for the development of efficient medications for specific targets. Among the drugs currently proposed for epigenetic therapy are histone deacetylase inhibitors and demethylating agents, which target chromatin in rapidly dividing tumor cells and restore normal cell functions (Karberg, 2009). The integration of the latest technological achievements in whole-genome microarray expression profiling and chromatin immunoprecipitation-based sequencing (ChIP-seq) methods will be instrumental in the development of epigenetic drugs with greater specificity.…”

HDAC Inhibition in Lupus Models

“…In SLE, several alleles have been identified as risk factors including major histocompatibility complex region, IFN-signaling molecules, transduction signaling genes, components of the complement cascade and others (33)(34)(35)(36). Many of the SLE susceptibility genes also are associated with pathways regulating other autoimmune disorders, including rheumatoid arthritis (3,16,37). Direct comparison of identical twins provides an excellent model for identifying epigenetic factors that may play a role in disease pathogenesis.…”

“…Owing to their conserved catalytic domain, HDACs have been actively targeted as a therapeutic target. The reversible nature of these epigenetic maintainer enzymes provides a plausible treatment for skewing the differentiation of a cell type to a different phenotype and may provide viable treatment options to ameliorate disease (15,16). Indeed, the vast majorities of studies with pan HDACi in cell culture systems and in vivo disease models of cancers have resulted in FDA approval of these classes of drugs for the treatment of cancer (17).…”

Insights in human epigenomic dynamics through comparative primate analysis

“…As such, the inactivated Xchromosome in females is not reactivated on the administration of the demethylating drug azacytidine [117]. Regulatory factors including TFs and long noncoding RNA (lnc-RNA) are proposed to play a significant role in human evolution [118].…”