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.
