Epigenetic Modifications in Tumor Suppressor Genes (TSG) 19for resistance to drugs in tumor cells. Then, the alternate use of conventional
anticancer drugs with epigenetic drugs has been proposed.
The effectiveness of DNMT and HDAC inhibitors in the treatment of
various human cancers is being analyzed in several clinical trials. So, it has
been demonstrated the effectiveness of the 5-aza-2’-deoxycytidine (5-aza- 2 -
dC; decitabina), a DNMT inhibitor that causes the DNA demethylation or
hemi-demethylation, in the treatment of myelodysplastic syndromes and
leukemias 17, 18. Several preclinical and clinical studies have demonstrated
the efficacy of epigenetic treatment for the lymphoma non-Hodgkin (NHL)
and some specific inhibitors of DNMT (5-aza-cytidine and 5-aza-
deoxicitidine) and HDAC (vorinostat and romidepsin) have been approved for
clinical use. In vitro, it has been shown that 5-aza- 2 - dC reduces the
methylation of PRDM2, PRDM5 PRDM16 genes in adenocarcinoma and lung
squamous cell carcinoma, decreasing tumor proliferation 11 . Another
DNMT1inhibitor, 3,6-dihydroxyflavone (DHF), inhibits carcinogens in human
breast epithelial cells 19 .
Several HDAC inhibitors have been developed up to the present. The
inhibition of these enzymes leads to the acetylation of histones and
transcription of genes, such as regulators of the cell cycle. The
suberoylanilide hydroxamic acid also known as Vorinostat, is a HDAC
inhibitor used for the treatment of patients with cutaneous T cell lymphoma
that do not respond or are refractory to conventional chemotherapy 18 .
Vorinostat is also being analyzed for the treatment of other types of cancer.
Given the close interrelationship between DNA methylation and histone
modifications in TSG transcription inhibition, the combined use of HDAC and
DNMT inhibitors that could have a synergistic effect in the treatment of cancer
is being analyzed. So, it was demonstrated that the combination of
hypomethylating agents and histone deacetylase inhibitors produce marked
synergy in preclinical models of T-cell lymphoma 20 .
CONCLUSIONS
Epigenetic modifications may have implications of clinical relevance, in
the diagnosis, prevention, and treatment of cancer. The knowledge of the
epigenetic patterns in different regions of the human genome will allow us to
establish an association with the development of different tumors. Also, due to
the reversible character of epigenetic changes, the design of therapeutic