scholarly journals Role of Histone Deacetylase Inhibitors in Relapsed Refractory Multiple Myeloma: A Focus on Vorinostat and Panobinostat

2015 ◽  
Vol 35 (12) ◽  
pp. 1173-1188 ◽  
Author(s):  
Salma Afifi ◽  
Angela Michael ◽  
Mahshid Azimi ◽  
Mabel Rodriguez ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Refractory Multiple Myeloma

The role of histone deacetylase inhibitors in patients with relapsed/refractory multiple myeloma

2013 ◽  
Vol 55 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Roman Hajek ◽  
David Siegel ◽  
Robert Z. Orlowski ◽  
Heinz Ludwig ◽  
Antonio Palumbo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Refractory Multiple Myeloma

scholarly journals Monoclonal Antibodies versus Histone Deacetylase Inhibitors in Combination with Bortezomib or Lenalidomide plus Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma: An Indirect-Comparison Meta-Analysis of Randomized Controlled Trials

2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Yanhua Zheng ◽  
Hongyuan Shen ◽  
Li Xu ◽  
Juan Feng ◽  
Hailong Tang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Complete Response ◽  
Refractory Multiple Myeloma ◽  
Grade 3

During the past decades, agents with novel mechanisms of action, such as monoclonal antibodies (MAbs) and histone deacetylase inhibitors (HDACis) have been applied to treat relapsed or refractory multiple myeloma (RRMM). The treatment outcomes of MAbs versus HDACi in combination with bortezomib or lenalidomide plus dexamethasone remain unknown. We conducted this meta-analysis to compare indirectly the efficacy and safety of MAbs and HDACis in combination with bortezomib or lenalidomide plus dexamethasone. Six trials (eight articles) were included in the meta-analysis with 3270 RRMM patients enrolled. We synthesized hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), risk ratios (RRs) for complete response (CR),very good partial response (VGPR), overall response (OR), progressive disease plus stable disease (PD + SD) and common at least grade 3 adverse events, and their corresponding 95%confidence intervals (95% CI). Treatment with MAbs in combination with bortezomib or lenalidomide plus dexamethasone resulted in longer PFS (HR 0.83, 95% CI: 0.66–0.98), fewer incidences of at least grade 3 thrombocytopenia (RR 0.35, 95% CI: 0.23–0.53), neutropenia (RR 0.70, 95% CI: 0.51–0.96), and sense of fatigue (RR 0.37, 95% CI: 0.17–0.82) than HDACis. The daratumumab plus bortezomib or lenalidomide and dexamethasone might significantly improve PFS in comparison with HDACis plus bortezomib or lenalidomide and dexamethasone (HR 0.55, 95% CI: 0.40–0.74). In conclusion, MAbs may be superior to HDACis in achieving longer PFS and may be better tolerated when in combination therapy with bortezomib or lenalidomide plus dexamethasone.

scholarly journals Epigenetic Targeting of Autophagy via HDAC Inhibition in Tumor Cells: Role of p53

2018 ◽  
Vol 19 (12) ◽  
pp. 3952 ◽  
Author(s):  
Maria Mrakovcic ◽  
Lauren Bohner ◽  
Marcel Hanisch ◽  
Leopold F. Fröhlich
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Histone Deacetylase ◽  
Stress Responses ◽  
Histone Deacetylase Inhibitors ◽  
Tumor Therapy ◽  
Regulatory System ◽  
Anticancer Activities ◽  
Mutational Status

Tumor development and progression is the consequence of genetic as well as epigenetic alterations of the cell. As part of the epigenetic regulatory system, histone acetyltransferases (HATs) and deacetylases (HDACs) drive the modification of histone as well as non-histone proteins. Derailed acetylation-mediated gene expression in cancer due to a delicate imbalance in HDAC expression can be reversed by histone deacetylase inhibitors (HDACi). Histone deacetylase inhibitors have far-reaching anticancer activities that include the induction of cell cycle arrest, the inhibition of angiogenesis, immunomodulatory responses, the inhibition of stress responses, increased generation of oxidative stress, activation of apoptosis, autophagy eliciting cell death, and even the regulation of non-coding RNA expression in malignant tumor cells. However, it remains an ongoing issue how tumor cells determine to respond to HDACi treatment by preferentially undergoing apoptosis or autophagy. In this review, we summarize HDACi-mediated mechanisms of action, particularly with respect to the induction of cell death. There is a keen interest in assessing suitable molecular factors allowing a prognosis of HDACi-mediated treatment. Addressing the results of our recent study, we highlight the role of p53 as a molecular switch driving HDACi-mediated cellular responses towards one of both types of cell death. These findings underline the importance to determine the mutational status of p53 for an effective outcome in HDACi-mediated tumor therapy.

Potential Role of Histone Deacetylase Inhibitors in Mesothelioma: Clinical Experience with Suberoylanilide Hydroxamic Acid

2006 ◽  
Vol 7 (4) ◽  
pp. 257-261 ◽  
Author(s):  
Lee M. Krug ◽  
Tracy Curley ◽  
Lawrence Schwartz ◽  
Stacie Richardson ◽  
Paul Marks ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Clinical Experience ◽  
Hydroxamic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Potential Role ◽  
Suberoylanilide Hydroxamic Acid

The potential of histone deacetylase inhibitors for the treatment of multiple myeloma

2008 ◽  
Vol 49 (3) ◽  
pp. 385-387 ◽  
Author(s):  
H. Miles Prince ◽  
Mark Bishton ◽  
Simon Harrison
Keyword(s):  
Multiple Myeloma ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors
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