Reviews on Recent Clinical Trials

Alberto Zaniboni  
Oncologia Medica, Fondazione Poliambulanza
Brescia
Italy

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Review: Recent Clinical Trials in Epigenetic Therapy

Author(s): Yasuhiro Oki and Jean-Pierre J. Issa

Affiliation: Department of Leukemia,University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd,Box 428, Houston, TX, 77030, USA.

Abstract:

Epigenetic factors such as DNA methylation and histone deacetylation are known to contribute to the malignant transformation of cells by silencing critical genes. Drugs that inhibit DNA methyltransferases or histone deacetylases were shown to have the potential to reactivate silenced genes and induce differentiation or apoptosis of malignant cells. The most intensively studied class of such agents is DNA methyltransferase inhibitors, including 5-azacytidine (azacitidine) and 5-aza-2-deoxycytidine (decitabine). In 2004, azacitidine was approved for the treatment of myelodysplastic syndrome on the basis of phase II and III studies that showed a response rate (complete and partial responses) of 15%. Azacitidine is also being evaluated in clinical trials for other malignant diseases. Decitabine has response rates of 17-49% in myelodysplastic syndrome in multiple phase II and III studies and also activity in acute and chronic myelogenous leukemia. Histone deacetylase inhibitors belong to another class of epigenetic modifying agents that include depsipeptide, butyrate derivatives, suberoylanilide hydroxamic acid and valproic acid. No agent in this class has been studied in a phase III trial, but several agents have been or are being studied in phase II trials. Further research is needed to determine the appropriate patient selection and dosing schedules.

Keywords: Cancer, Clinical trial, Epigenetic, DNA methylation, Histone acetylation

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Article Details

VOLUME: 1
ISSUE: 2
Page: [169 - 182]
Pages: 14
DOI: 10.2174/157488706776876490
Price: $58