TY - JOUR
T1 - The safety profile of vorinostat (suberoylanilide hydroxamic acid) in hematologic malignancies
T2 - A review of clinical studies
AU - Duvic, Madeleine
AU - Dimopoulos, Meletios
N1 - Funding Information:
This review was sponsored by Merck & Co., Inc. , Kenilworth, NJ, USA. The sponsor had no role in content development or in the decision to submit the manuscript for publication. The authors thank Dr. Lauren Pinter-Brown for critically reviewing the manuscript. Medical writing and editorial assistance were provided by Joseph J. Abrajano, PhD, and Kakuri M. Omari, PhD, of Integrus Scientific, a division of Medicus International New York (New York, NY). This assistance was funded by Merck & Co., Inc., Kenilworth, NJ. Mary E. Hanson, PhD of Merck & Co., Inc., Kenilworth, NJ, USA also provided writing assistance. Kristen Lewis and Carol Zecca of Merck & Co., Inc., Kenilworth, NJ provided editorial assistance. The authors were fully responsible for all content and editorial decisions.
Publisher Copyright:
© 2016.
PY - 2016
Y1 - 2016
N2 - Histone acetyltransferases and histone deacetylases (HDACs) are multifunctional enzymes that posttranslationally modify both histone and nonhistone acetylation sites, affecting a broad range of cellular processes (e.g., cell cycle, apoptosis, and protein folding) often dysregulated in cancer. HDAC inhibitors are small molecules that directly interact with HDAC catalytic sites preventing the removal of acetyl groups, thereby counteracting the effects of HDACs. Since the first HDAC inhibitor, valproic acid, was investigated as a potential antitumor agent, there have been a number of other HDAC inhibitors developed to improve efficacy and safety. Despite significant progress in the management of patients with hematologic malignancies, overall survival is still poor. The discovery that HDACs may play a role in hematologic malignancies and preclinical studies showing promising activity with HDAC inhibitors in various tumor types, led to clinical evaluation of HDAC inhibitors as potential treatment options for patients with advanced hematologic malignancies. The Food and Drug Administration has approved two HDAC inhibitors, vorinostat (2006) and romidepsin (2009), for the treatment of cutaneous T-cell lymphoma. This review highlights the safety of HDAC inhibitors currently approved or being investigated for the treatment of hematologic malignancies, with a specific focus on the safety experience with vorinostat in cutaneous T-cell lymphoma.
AB - Histone acetyltransferases and histone deacetylases (HDACs) are multifunctional enzymes that posttranslationally modify both histone and nonhistone acetylation sites, affecting a broad range of cellular processes (e.g., cell cycle, apoptosis, and protein folding) often dysregulated in cancer. HDAC inhibitors are small molecules that directly interact with HDAC catalytic sites preventing the removal of acetyl groups, thereby counteracting the effects of HDACs. Since the first HDAC inhibitor, valproic acid, was investigated as a potential antitumor agent, there have been a number of other HDAC inhibitors developed to improve efficacy and safety. Despite significant progress in the management of patients with hematologic malignancies, overall survival is still poor. The discovery that HDACs may play a role in hematologic malignancies and preclinical studies showing promising activity with HDAC inhibitors in various tumor types, led to clinical evaluation of HDAC inhibitors as potential treatment options for patients with advanced hematologic malignancies. The Food and Drug Administration has approved two HDAC inhibitors, vorinostat (2006) and romidepsin (2009), for the treatment of cutaneous T-cell lymphoma. This review highlights the safety of HDAC inhibitors currently approved or being investigated for the treatment of hematologic malignancies, with a specific focus on the safety experience with vorinostat in cutaneous T-cell lymphoma.
KW - Clinical trial
KW - HDAC
KW - Hematologic malignancies
KW - Histone deacetylase inhibitors
KW - Safety
KW - Vorinostat
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U2 - 10.1016/j.ctrv.2015.04.003
DO - 10.1016/j.ctrv.2015.04.003
M3 - Review article
C2 - 26827693
AN - SCOPUS:84962019062
SN - 0305-7372
VL - 43
SP - 58
EP - 66
JO - Cancer treatment reviews
JF - Cancer treatment reviews
ER -