New insights into the treatment of multiple myeloma with histone deacetylase inhibitors

Michele Cea, Antonia Cagnetta, Marco Gobbi, Franco Patrone, Paul G. Richardson, Teru Hideshima, Kenneth C. Anderson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)734-744
Number of pages11
JournalCurrent Pharmaceutical Design
Volume19
Issue number4
Publication statusPublished - 2013

Keywords

  • Apoptosis
  • HDACIs
  • Multiple myeloma
  • Novel therapy
  • Proteasome inhibitor

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

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