Histone deacetylase inhibitor and demethylating agent chromatin compaction and the radiation response by cancer cells.
It now appears that epigenetics plays a central role in transformation, both in vitro and in vivo. The expression and regulation of DNA methylation and the subsequent chromatin structure are significantly altered in tumor cells, suggesting a direct role in the process of in vivo cellular transformation. If epigenetics and posttranslational modifications of histones play a role in transformation, then it seems logical that the genes regulating chromatin compaction may also be molecular targets and markers in profiling tumor cell resistance. Local remodeling of chromatin is a key step in the regulation of gene expression, and altering the expression of these genes might also favorably alter how tumor cells respond to anticancer agents. Several new agents that alter chromatin compaction, either methyltransferase or histone deacetylases inhibitors, are progressing through clinical trials and have shown promising preclinical interactions when combined with radiation. In this review, we discuss the potential for histone deacetylases inhibitors as radiosensitizing agents.
Bar-Sela
Gil
G
Radiation Oncology Branch, Radiation Oncology Sciences Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jacobs
Kristi Muldoon
KM
Gius
David
D
D042002:Chromatin Assembly and Disassembly / Q000187:drug effects* / Q000528:radiation effects*; D019175:DNA Methylation / Q000187:drug effects* / Q000528:radiation effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D011838:Radiation-Sensitizing Agents