Epigenetics and cancer treatment.
In addition to the genetic alterations, observed in cancer cells, are mitotically heritable changes in gene expression not encoded by the DNA sequences, which are referred to as epigenetic changes. DNA methylation is among the most studied epigenetic mechanisms together with various histone modifications involved in chromatin remodeling. As opposed to genetic lesions, the epigenetic changes are potentially reversible by a number of small molecules, known as epi-drugs. This review will focus on the biological mechanisms underlying the epigenetic silencing of tumor suppressor genes observed in cancer cells, and the targeted molecular strategies that have been investigated to reverse these aberrations. In particular, we will focus on DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) as epigenetic targets for cancer treatment. A synergistic effect of a combined use of DNMT and HDAC inhibitors has been observed. Moreover, epi-drugs sensitize multiple different cancer cells to a large variety of other treatment strategies. In particular, we have focused on the ability of DNMT and HDAC inhibitors to restore the estrogen receptor alpha (ERalpha) activity in breast cancer. Finally, we will discuss the potential of DNA methylation changes as biomarkers to be used in diverse areas of cancer treatment, especially for predicting response to treatment with DNMT and HDAC inhibitors.
Kristensen
Lasse Sommer
LS
Institute of Human Genetics, The Bartholin Building, University of Aarhus, 8000 Aarhus C, Denmark.
Nielsen
Helene Myrtue
HM
Hansen
Lise Lotte
LL
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D019175:DNA Methylation / Q000187:drug effects; D016503:Drug Delivery Systems; D004357:Drug Synergism; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics
D056572:Histone Deacetylase Inhibitors; D004248:DNA (Cytosine-5-)-Methyltransferases