Histone deacetylase inhibitors in cancer therapy: Biological and clinical implications.

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Influencing epigenetic tumorigenic modifications is an exciting strategy for anticancer drugdevelopment. Acetylation/deacetylation of histones, a process catalysed by histone acetyltransferases (HATs) and Histone deacetylases (HDACs) respectively, is an important modality to regulate chromatin remodelling and consequent gene expression. Aberrant expression of HDACs and disrupted activities of HATs have been found in several tumor types, implicating their involvement in cancer.Histone deacetylase inhibitors (HDACi) represent a new and promising class of anti-tumor drugsthat influence gene expression by enhancing the acetylation of histones. HDAC inhibitors have been shown to have potent anticancer activities due to arrest of cell proliferation and apoptosis induction.Interestingly, malignant cells appear more sensitive to the proapoptotic effects of HDACi,underscoring the therapeutic potential of these agents. Several HDACi are currently under clinical investigation, including vorinostat (SAHA), a compound which has been recently approved in the therapy of specific lymphoma types.In this chapter, the results of published data on the effects of HDACi in different tumor types are reviewed, with a focus on the molecular mechanisms of anti-tumor efficacy and clinicalapplications.
Lingua originaleEnglish
EditoreResearch Signpost
ISBN (stampa)978-81-308-0201-5
Stato di pubblicazionePublished - 2007


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