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Epigenetic drugs as pleiotropic agents in cancer treatment: Biomolecular aspects and clinical applications
Author(s) -
Sigalotti Luca,
Fratta Elisabetta,
Coral Sandra,
Cortini Enzo,
Covre Alessia,
Nicolay Hugues J.M.,
Anzalone Lucia,
Pezzani Laura,
Di Giacomo Anna Maria,
Fonsatti Ester,
Colizzi Francesca,
Altomonte Maresa,
Calabrò Luana,
Maio Michele
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21066
Subject(s) - epigenetics , biology , carcinogenesis , dna methylation , histone , cancer , epigenetic regulation of neurogenesis , cancer epigenetics , cancer research , genetics , gene , gene expression , chromatin remodeling , histone methyltransferase
In the last three decades huge efforts have been made to characterize genetic defects responsible for cancer development and progression, leading to the comprehensive identification of distinct cellular pathways affected by the alteration of specific genes. Despite the undoubtable role of genetic mechanisms in triggering neoplastic cell transformation, epigenetic modifications (i.e., heritable changes of gene expression that do not derive from alterations of the nucleotide sequence of DNA) are rapidly emerging as frequent alterations that often occur in the early phases of tumorigenesis and that play an important role in tumor development and progression. Epigenetic alterations, such as modifications in DNA methylation patterns and post‐translational modifications of histone tails, behave extremely different from genetic modifications, being readily revertable by “epigenetic drugs” such as inhibitors of DNA methyl transferases and inhibitors of histone deacetylases. Since epigenetic alterations in cancer cells affect virtually all cellular pathways that have been associated to tumorigenesis, it is not surprising that epigenetic drugs display pleiotropic activities, being able to concomitantly restore the defective expression of genes involved in cell cycle control, apoptosis, cell signaling, tumor cell invasion and metastasis, angiogenesis and immune recognition. Prompted by this emerging clinical relevance of epigenetic drugs, this review will focus on the large amount of available data, deriving both from in vitro experimentations and in vivo pre‐clinical and clinical studies, which clearly indicate epigenetic drugs as effective modifiers of cancer phenotype and as positive regulators of tumor cell biology with a relevant therapeutic potential in cancer patients. J. Cell. Physiol. 212: 330–344, 2007. © 2007 Wiley‐Liss, Inc.

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