Epigenetic control of gene expression: Potential implications for cancer treatment
Section snippets
Background
Epigenetics means “beyond genetic” or “other than genetic” and is defined as a group of inheritable changes in gene expression occurring without alterations in DNA sequence. In the eukaryotic nucleus, DNA is compacted in a structure defined as chromatin, whose basic unit is the nucleosome. Each nucleosome is formed by a multiproteic complex named “histone”, surrounded by about 145–147 pairs of DNA bases. Histone is an octamer constituted by four pairs of proteins, called H3, H4, H2A and H2B.
Epigenetics and cancer
Cancer is the result of DNA aberrations causing deregulation of cell cycle, apoptosis and cell survival. DNA mutations involving oncogenes (OG) the genes able to promote cell survival and tumor suppressor genes (TSG) are well known to be responsible for cancer initiation, promotion and progression. Nevertheless, recent data have suggested a crucial role for epigenetic mechanisms in cancer development. Indeed, carcinogenesis, cannot be explained only by genetic alterations, but also involve
Drugs targeting the epigenetic code
Epigenetic changes are often found in both solid and hematological malignancies. Interestingly, epigenetic changes are reversible modifications. This feature makes them an attractive target for cancer therapy. Defining and restoring the normal and pre-existent epigenetic landscape has became the focus of active investigation and several “epigenetic drugs” have been tested in the clinical setting. An effective anticancer treatment requires the identification of the target and the demonstration
Conclusions
Cancer has a very complex pathogenesis and pathophysiology and its development requires the accumulation of multiple genomic aberrations. These changes can involve OGs, causing their hyper-activation, or TSGs, inducing their silencing, but the final result is cell-cycle deregulation and apoptosis inhibition. DNA mutations alone are probably important for “iniziation” of carcinogenesis. The following step of carcinogenesis is named “promotion”, namely the accumulation of other DNA changes which
Author contributions
Dr Perri and Dr. Della Vittoria Scarpati designed the work. All the authors collected the data. Dr Perri wrote the paper and Dr Giuliano edited the manuscript.
Conflicts of interest
The authors declare no conflict of interest.
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