Document Detail


New insights into the treatment of multiple myeloma with histone deacetylase inhibitors.
MedLine Citation:
PMID:  23016853     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Michele Cea; Antonia Cagnetta; Marco Gobbi; Franco Patrone; Paul G Richardson; Teru Hideshima; Kenneth C Anderson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current pharmaceutical design     Volume:  19     ISSN:  1873-4286     ISO Abbreviation:  Curr. Pharm. Des.     Publication Date:  2013  
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-07-08     Revised Date:  2013-08-15    
Medline Journal Info:
Nlm Unique ID:  9602487     Medline TA:  Curr Pharm Des     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  734-44     Citation Subset:  IM    
Affiliation:
Department of Medical Oncology, Dana-Farber Cancer Institute, M551, 450 Brookline Avenue, Boston, MA 02115, USA. michele_cea@dfci.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*,  therapeutic use
Drug Synergism
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Histone Deacetylase Inhibitors / pharmacology*,  therapeutic use
Humans
Hydroxamic Acids / pharmacology,  therapeutic use
Indoles / pharmacology,  therapeutic use
Molecular Targeted Therapy
Multiple Myeloma / drug therapy*,  enzymology,  genetics
Tumor Microenvironment
Grant Support
ID/Acronym/Agency:
P01 CA078378/CA/NCI NIH HHS; P01 CA155258/CA/NCI NIH HHS; P50 CA100707/CA/NCI NIH HHS; R0-1 CA-50947/CA/NCI NIH HHS; R0-1 CA-73878/CA/NCI NIH HHS; R01 CA050947/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/Indoles; 0/panobinostat; 149647-78-9/vorinostat

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