title: Targeting Histone Deacetylases in Diseases: Where Are We?
abstract: CONCLUSIONS
  Epigenetic inactivation of pivotal genes involved in cell growth is a hallmark of human pathologies, in particular cancer. Histone acetylation balance obtained through opposing actions of histone deacetylases (HDACs) and histone acetyltransferases is one epigenetic mechanism controlling gene expression and is, thus, associated with disease etiology and progression. Interfering pharmacologically with HDAC activity can correct abnormalities in cell proliferation, migration, vascularization, and death.
  
  
  BACKGROUND
  Histone deacetylase inhibitors (HDACi) represent a new class of cytostatic agents that interfere with the function of HDACs and are able to increase gene expression by indirectly inducing histone acetylation. Several HDACi, alone or in combination with DNA-demethylating agents, chemopreventive, or classical chemotherapeutic drugs, are currently being used in clinical trials for solid and hematological malignancies, and are, thus, promising candidates for cancer therapy.
  
  
  RESULTS
  (i) Non-specific (off-target) HDACi effects due to activities unassociated with HDAC inhibition. (ii) Advantages/disadvantages of non-selective or isoform-directed HDACi. (iii) Limited number of response-predictive biomarkers. (iv) Toxicity leading to dysfunction of critical biological processes.
  
  
  CONCLUSIONS
  Selective HDACi could achieve enhanced clinical utility by reducing or eliminating the serious side effects associated with current first-generation non-selective HDACi. Isoform-selective and pan-HDACi candidates might benefit from the identification of biomarkers, enabling better patient stratification and prediction of response to treatment.
authors.affiliation: 1 Department of Biochemistry, Biophysics, and General Pathology, Seconda Università degli Studi di Napoli , Napoli, Italy .
authors.forename: Rosaria
authors.initials: R
authors.lastname: Benedetti
authors.affiliation: 1 Department of Biochemistry, Biophysics, and General Pathology, Seconda Università degli Studi di Napoli , Napoli, Italy .
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Conte
authors.affiliation: 1 Department of Biochemistry, Biophysics, and General Pathology, Seconda Università degli Studi di Napoli , Napoli, Italy .|2 Istituto di Genetica e Biofisica "Adriano Buzzati-Traverso," Napoli, Italy .
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
mesh_terms: D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000145:classification / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases