title: Therapeutic strategies to enhance the anticancer efficacy of histone deacetylase inhibitors.
abstract: Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi) has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.
authors.affiliation: Department of Pediatrics Research, Children's Cancer Hospital, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Claudia P
authors.initials: CP
authors.lastname: Miller
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Singh
authors.forename: Nilsa
authors.initials: N
authors.lastname: Rivera-Del Valle
authors.forename: Christa A
authors.initials: CA
authors.lastname: Manton
authors.forename: Joya
authors.initials: J
authors.lastname: Chandra
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004249:DNA Damage / Q000187:drug effects; D004359:Drug Therapy, Combination; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D061988:Proteasome Inhibitors; D018714:Radiotherapy, Adjuvant; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D006655:Histone Deacetylases