title: New insights into the treatment of multiple myeloma with histone deacetylase inhibitors.
abstract: Multiple Myeloma (MM) is a common hematologic malignancy of plasma cells representing an excellent model of epigenomics dysregulation in human disease. Importantly, these findings, in addition to providing a better understanding of the underlying molecular changes leading to this malignance, furnish the basis for an innovative therapeutic approach. Histone deacetylase inhibitors (HDACIs), including Vorinostat and Panobinostat, represent a novel class of drugs targeting enzymes involved in epigenetic regulation of gene expression, which have been evaluated also for the treatment of multiple myeloma. Although the clinical role in this setting is evolving and their precise utility remains to be determined, to date that single-agent anti-MM activity is modest. More importantly, HDACIs appear to be synergistic both in vitro and in vivo when combined with other anti-MM agents, mainly proteasome inhibitors including bortezomib. The molecular basis underlying this synergism seems to be multifactorial and involves interference with protein degradation as well as the interaction of myeloma cells with microenvironment. Here we review molecular events underling antitumor effects of HDACIs and the most recent results of clinical trials in relapsed and refractory MM.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, M551, 450 Brookline Avenue, Boston, MA 02115, USA. michele_cea@dfci.harvard.edu
authors.forename: Michele
authors.initials: M
authors.lastname: Cea
authors.forename: Antonia
authors.initials: A
authors.lastname: Cagnetta
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.forename: Franco
authors.initials: F
authors.lastname: Patrone
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Teru
authors.initials: T
authors.lastname: Hideshima
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000077767:Panobinostat; D059016:Tumor Microenvironment; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000077337:Vorinostat; D000077767:Panobinostat