La saga des inhibiteurs des histone-desacetylases: de la TSA au SAHA

Acetylation; Apoptosis; Cell Cycle/physiology; Enzyme Inhibitors/pharmacology/therapeutic use; Histone Deacetylase Inhibitors; Histones/physiology; Humans; Neoplasms/drug therapy/physiopathology

Abstract :

[en] Histone-deacetylase inhibitors (HDCACi) represent a new class of antitumor agents currently in clinical development. They target a family of enzymes which catalyse histone acetylation modifications, in particular for histones H2A, H2B, H3 and H4. These proteins stabilize the nucleosome core, fundamental unity of chromatin which represents the first level of DNA nuclear compaction. The balance of histone acetylation is maintained by histone-acetyltransferases (HAT) and histone-deacetylases (HDAC) which play an important role in gene transcription. Alterations of HDACs were identified in tumor cells and contribute to the massive perturbations of gene expression in numerous tumors. HDAC inhibition leads to differentiation, cell cycle arrest and apoptosis in tumor cells. HDACi efficiently prevent tumor growth in a variety of in vivo preclinical models. Several structurally distinct classes of HDACi have entered in clinical trials and a significant antitumor activity was reported in several cases. However, a better understanding of the biological effects of this class of enzymes is mandatory for the successful development of these new antitumoral agents. In this review, are exposed the main drug candidates in clinical development. In the near future, it will be interesting to define direct relationships between specific inhibition of one or several HDAC and the subsequent HDAC-dependent antitumor effects to define a new generation of specific histone-deacetylase inhibitors.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Peixoto, Paul

Lansiaux, Amelie

Language :

French

Title :

La saga des inhibiteurs des histone-desacetylases: de la TSA au SAHA

Alternative titles :

[en] Histone-deacetylases inhibitors: from TSA to SAHA

Publication date :

2006

Journal title :

Bulletin du Cancer

ISSN :

0007-4551

eISSN :

1769-6917

Publisher :

John Libbey Eurotext, Montrouge, France

Volume :

Issue :

Pages :

27-36

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 03 March 2011

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