title: An overview of investigational Histone deacetylase inhibitors (HDACis) for the treatment of non-Hodgkin's lymphoma.
abstract: BACKGROUND
  Histone acetylation alters DNA transcription and protein expression. Aberrant acetylation is seen in tumor cells. Histone deacetylase inhibitors (HDACis) act by modifying gene expression and are the newest class of drugs shown to be promising in patients with several malignancies including relapsed and/or refractory lymphoma. Multiple HDACis are currently under various phases of clinical trials for the treatment of Non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  This review discusses the mechanism of histone acetyl transferases (HAT's), histone deacetylases (HDAC's) and their role in B - and T-cell malignancies with a particular focus on the mechanism of action and clinical application of HDACis in NHL. Discussion includes: HDACi's like vorinostat, romidepsin, belinostat, panobinostat, entinostat and chidamide; pivotal clinical trials leading to the approval of HDACis in NHL; ongoing active clinical trials and combination therapies with novel agents.
  
  
  CONCLUSIONS
  Relapsed and or refractory lymphoma poses a challenge to the clinician given the poor outcomes. HDACis show promising clinical activity in patients with relapsed/refractory NHL. Active pursuit of developing newer HDACis and clinical trials using combination therapies that help understand the molecular characteristics and synergistic actions of these agents is warranted. This would help improve efficacy, drug tolerability and expand the horizon of these novel agents.
authors.affiliation: a Department of Malignant Hematology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA.
authors.forename: Susmitha
authors.initials: S
authors.lastname: Apuri
authors.affiliation: a Department of Malignant Hematology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA.
authors.forename: Lubomir
authors.initials: L
authors.lastname: Sokol
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases
keywords: Histone deacetylase inhibitors; and clinical trials; mechanism of action; non-hodgkin’s lymphoma