DNA demethylating agents and histone deacetylase inhibitors in hematologic malignancies.
The pivotal role of aberrant promoter methylation in gene silencing and cancer development has fueled the interest in DNA methyltransferase inhibitors as novel anticancer drugs. Modulation of gene expression through targeting of epigenetic marks is one of the emerging and promising strategies that has demonstrated successful clinical outcome in hematologic malignancies. Epigenetic modifiers, including DNA methyltransferase inhibitors and histone deacetylase inhibitors, have demonstrated significant clinical activity; several are or are likely to soon be approved by the U.S. Food and Drug Administration. However, the exact mechanism of the clinical response achieved is not fully understood. This review focuses on the pharmacology of the known DNA methyltransferase and histone deacetylase inhibitors and their potential as promising anticancer drugs.
Fandy
Tamer E
TE
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
Carraway
Hetty
H
Gore
Steven D
SD
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006801:Humans
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D015254:DNA Modification Methylases