Abstract
Epigenetic alterations complement genetic mutations as a molecular mechanism leading
to cell transformation, and maintenance of the cancer phenotype. Of note, they are
reversible by pharmacological manipulation of the enzymes responsible for chromatin
modification: indeed, epigenetic drugs (histone deacetylase inhibitors and DNA demethylating
agents) are currently on the market, inducing proliferative arrest and death of tumor
cells. These drugs, however, have been effective only in a few tumor types: the lack
of consistent clinical results is mainly due to their use in a poorly targeted approach,
since the epigenetic alterations present in cancer cells are mostly unknown. In a
few cases (notably, leukemias expressing RAR and MLL fusion proteins), the molecular
mechanisms underlying tumor-selective and tumor-specific epigenetic alterations have
started to be deciphered. These studies are revealing a dazzling complexity in the
mechanisms leading to alterations of the epigenome, and the need of combination therapies
targeting different chromatin modifiers to reach an effective reversion of epigenetic
alterations.
Keywords
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Article info
Publication history
Published online: April 06, 2009
Accepted:
March 3,
2009
Received:
February 24,
2009
Identification
Copyright
© 2009 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
