Epi-drugs to fight cancer: from chemistry to cancer treatment, the road ahead.
In addition to genetic events, a variety of epigenetic events have been widely reported to contribute to the onset of many diseases including cancer. DNA methylation and histone modifications (such as acetylation, methylation, sumoylation, and phosphorylation) involving chromatin remodelling are among the most studied epigenetic mechanisms for regulation of gene expression leading, when altered, to some diseases. Epigenetic therapy tries to reverse the aberrations followed to the disruption of the balance of the epigenetic signalling ways through the use of both natural compounds and synthetic molecules, active on specific epi-targets. Such epi-drugs are, for example, inhibitors of DNA methyltransferases, histone deacetylases, histone acetyltransferases, histone methyltransferases, and histone demethylases. In this review we will focus on the chemical aspects of such molecules, joined to their effective (or potential) application in cancer therapy.
Mai
Antonello
A
Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, 00185 Roma, IT, Italy. antonello.mai@uniroma1.it
Altucci
Lucia
L
D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D044127:Epigenesis, Genetic; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D015254:DNA Modification Methylases; D051548:Histone Acetyltransferases; D037761:Sirtuins; D006655:Histone Deacetylases