title: Targeting epigenetic networks with polypharmacology: a new avenue to tackle cancer.
abstract: The term 'epigenetic' fuses old and new concepts that refer to the modulation of gene expression in cellular heritability, fate, development and programming-reprogramming other than the DNA sequence itself. Epigenetic control of transcription is regulated by enzymes that mediate covalent modifications at gene-regulatory regions and histone proteins around which chromosomal DNA is wound. Many of the enzymes that mediate chromatin epigenetic reactions are deregulated in diseases such as cancer. Thus, small-molecule inhibitors that target chromatin-modifying enzymes represent a novel option for treatment, and DNA methyltransferase and histone deacetylase inhibitors have been approved for cancer treatment. Moreover, other classes of epi-enzymes (MS-275, SAHA) have been demonstrated to have strong disease association, and are currently being targeted for modulation. An epigenetic poly-pharmacological approach targeting multiple chromatin-modifying enzymes may represent a 'smart' option to treat cancer versus the current view on the selective and single pharmacological targeting of epigenetic enzymes.
authors: Seconda Università di Napoli, Napoli, Italy.
authors: Gianluigi
authors: G
authors: Franci
authors: Marco
authors: M
authors: Miceli
authors: Lucia
authors: L
authors: Altucci
mesh_terms: D002843:Chromatin / Q000201:enzymology* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D019338:Polypharmacy; D037761:Sirtuins / Q000037:antagonists & inhibitors
chemical_list: D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D037761:Sirtuins