Rational design and development of radiation-sensitizing histone deacetylase inhibitors.
Histone deacetylases (HDACs) offer potentially attractive molecular targets for sensitizing cancers to treatment with radiation therapy. By affecting patterns of gene expression, differentiation, apoptosis, and enhanced responses to therapeutic agents may be induced in cancer cells. Here, we review the drug characteristics underlying design and screening of HDAC inhibitors with a focus on radiation-sensitizing properties. Radiation-sensitizing capacities have been observed in three model systems, squamous carcinoma of head and neck origin (SQ-20B), prostate adenocarcinoma (PC-3), and breast adenocarcinoma (MCF7). Cell-type specificities in radiation-sensitizing properties have been observed. Mechanisms underlying specificity are under investigation.
Jung
Mira
M
Department of Radiation Medicine, Georgetown University Medical Center, The Research Building, Room E202, Box 571482, 3970 Reservoir Road NW, Washington, DC 20057-1482, USA.
Kozikowski
Alan
A
Dritschilo
Anatoly
A
D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000737:chemistry* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D011838:Radiation-Sensitizing Agents