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Histone deacetylase inhibitors: highlight on epigenetic regulation


Bulletin du Cancer. Volume 97, Number 8, 917-35, août 2010, Synthèse

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Author(s) : N Pécuchet, T Cluzeau, C Thibault, N Mounier, S Vignot

Summary : HDAC, by modifiing relations between DNA and histones, are major proteins of the epigenetic regulation. They play part in the signal transduction and in many cellular processes: cell cycle control, apoptosis, protein degradation, angiogenesis, invasion and cell motility. In several models of cancer HDAC inhibitors (HDACIs) are able to up regulate tumor suppressing gene (p53, p21, pRB…) and to down regulate oncogenes (SRC, HIF-Iα,HER2…). Many inhibitors are currently in clinical development and promising results have been reported in cutaneous T cell lymphoma, Hodgkin's disease and non-hodgkin lymphoma. Combination with chemotherapy and molecular targeted agents seem to be effective in myeloma, lung cancer and myeloïd neoplasms. In this review, we focus on recent biologic and clinical data that highlitght the anti-neoplastic role of HDACIs.

Keywords : histone deacetylase, molecular targeted therapy, epigenetic regulation

 

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