title: Histone deacetylase inhibitors: emerging mechanisms of resistance.
abstract: The histone deacetylase inhibitors (HDIs) have shown promise in the treatment of a number of hematologic malignancies, leading to the approval of vorinostat and romidepsin for the treatment of cutaneous T-cell lymphoma and romidepsin for the treatment of peripheral T-cell lymphoma by the U.S. Food and Drug Administration. Despite these promising results, clinical trials with the HDIs in solid tumors have not met with success. Examining mechanisms of resistance to HDIs may lead to strategies that increase their therapeutic potential in solid tumors. However, relatively few examples of drug-selected cell lines exist, and mechanisms of resistance have not been studied in depth. Very few clinical translational studies have evaluated resistance mechanisms. In the current review, we summarize many of the purported mechanisms of action of the HDIs in clinical trials and examine some of the emerging resistance mechanisms.
authors: Medical Oncology Branch, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, United States. robeyr@mail.nih.gov
authors: Robert W
authors: RW
authors: Robey
authors: Arup R
authors: AR
authors: Chakraborty
authors: Agnes
authors: A
authors: Basseville
authors: Victoria
authors: V
authors: Luchenko
authors: Julian
authors: J
authors: Bahr
authors: Zhirong
authors: Z
authors: Zhan
authors: Susan E
authors: SE
authors: Bates
mesh_terms: D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D056572:Histone Deacetylase Inhibitors