Cutting Edge Therapies for Cancer in the 21st Century

Role of Epigenetic Alterations in the Pathogenesis of Cancer: Recent Clinical Trials in Epigenetic Therapy

Author(s): Caterina Cinti, Monia Taranta, Ilaria Naldi and Juan Carlos Trivino Pardo

Pp: 28-80 (53)

Doi: 10.2174/9781608058808114010005

* (Excluding Mailing and Handling)

Abstract

The pattern of gene expression can vary in each cell without changes in the DNA sequence. This is accomplished by reversible chemical modifications of the chromatin, which are generally indicated with the term “epigenetics”. Chromatin remodeling caused by DNA methylation and histone modifications, especially at the site of genes promoters, are the major epigenetic events enabling transcriptional regulation. It is known that alterations of epigenetic signals are important early events for cancer development. These changes profoundly influence gene expression and are at the basis of malignant transformation. Specific pathways of genes are proficiently turned on or off by cancer cells to achieve uncontrolled proliferation. Genes playing key roles in DNA damage responses, apoptosis signaling and DNA repair are in fact frequently silenced by epigenetic modifications, while those involved in cell proliferation are often overexpressed. But the appealing feature of epigenetic changes is that they can be potentially reverted. This peculiarity has opened the way to new therapeutic possibilities to fight tumors that might be collectively termed “epigenetic therapy”. Here we will discuss the basic aspects of epigenetic alterations, and in particular those events involving critical genes implicated in carcinogenesis, and the current relevance of DNA methyltransferase and histone deacetylase inhibitors for cancer therapy.


Keywords: Cancer, DNA, methylation, CpG islands, chromatin, eterochromatin, euchromatin, histones, histone deacetylase, histone acetylation, histone acetyltransferases, epigenetic therapy, demethylating agents, deacetylating agents, DNA methyltransferases, multi-drug resistance associated protein, clinical trials, metalloproteinases, inhibitor of metalloproteinase, computational epigenetics.

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