title: Panobinostat  for the treatment of multiple myeloma.
abstract: BACKGROUND
  Multiple myeloma (MM) is a B-cell malignancy characterized by proliferation of monoclonal plasma cells in the bone marrow. Although new therapeutic options have been introduced and response rates have improved in recent years, MM still remains incurable and new treatment options are urgently needed. The histone deacetylase inhibitors (HDACi) are a new class of anticancer agents in early clinical development in many malignancies including MM. HDACi target the enzyme histone deacetylase (HDAC) involved in the deacetylation of histone and non-histone cellular proteins that play important roles in epigenetic regulation of gene expression inducing death, apoptosis and cell cycle arrest in cancer cells. Panobinostat (LBH589) is a highly potent HDACi with demonstrated antitumor activities at low nanomolar concentration in several preclinical studies and its clinical efficacy is currently under investigation in several clinical trials.
  
  
  METHODS
  In this review the authors discuss the role of HDACs in the regulation of gene expression and the biological mechanisms mediating the anticancer effects of HDACi with particular focus on the recent development of panobinostat as anti-MM agent in preclinical and clinical studies.
  
  
  CONCLUSIONS
  As a 'multi-target' drug, panobinostat appears attractive as potential anti-MM therapeutic for its ability to modulate a variety of biological pathways essential in MM biology. This 'multi-target' property of panobinostat may also be one its major shortcomings, and a better understanding of its mechanisms of action and targets will permit to identify the best combination therapies that will ultimately overcome and improve outcomes in MM patients.
authors.affiliation: Division of Hematology and Bone Marrow Transplant, University of Calgary, Alberta, Canada.
authors.forename: Paola
authors.initials: P
authors.lastname: Neri
authors.forename: Nizar J
authors.initials: NJ
authors.lastname: Bahlis
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D007211:Indoles; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism; D000077767:Panobinostat
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat; D006655:Histone Deacetylases