Authors: Thomas B Tomasi William J Magner A Nazmul H Khan
Publish Date: 2006/05/06
Volume: 55, Issue: 10, Pages: 1159-1184
Abstract
According to the concept of immune surveillance the appearance of a tumor indicates that it has earlier evaded host defenses and subsequently must have escaped immunity to evolve into a fullblown cancer Tumor escape mechanisms have focused mainly on mutations of immune and apoptotic pathway genes However data obtained over the past few years suggest that epigenetic silencing in cancer may be as frequent a cause of gene inactivation as are mutations Here we discuss the evidence that tumor immune evasion is mediated by nonmutational epigenetic events involving chromatin and that epigenetics collaborates with mutations in determining tumor progression Since epigenetic changes are potentially reversible the relative contribution of mutations and epigenetics to the gene defects in any given tumor may be a factor in determining the efficacy of treatments We review new developments in basic chromatin mechanisms and in this context describe the rationale for the current use of epigenetic agents in cancer therapy and for a novel epigenetically generated tumor vaccine model We emphasize that epigenetic cancer treatments are currently a ‘bluntsword’ and suggest future directions for designing chromatinbased programs of potential value in the diagnosis and treatment of cancer
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