Histone deacetylase inhibitors in multiple myeloma: from bench to bedside.
Histone deacetylases (HDACs) deacetylate the lysine residues of both histones and non-histone proteins. Histone acetylation results in a loose local chromatin structure that regulates gene-specific transcription. Non-histone proteins can also be acetylated, leading to dynamic changes in their activity and stability. For these reasons, HDAC inhibition has emerged as a potential approach for the treatment of MM. Specifically, combination treatment with HDAC inhibitors and proteasome inhibitors or immunomodulatory drugs shows remarkable anti-MM activity in both preclinical and clinical settings. However, the clinical studies using non-selective HDAC inhibitors also cause unfavorable side effects in patients, leading us to develop more isoform- and/or class-selective HDAC inhibitors to enhance tolerability without diminishing anti-MM activity, thereby improving patient outcome in MM.
Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.
Takeshi
T
Harada
Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA. teru_hideshima@dfci.harvard.edu.
Teru
T
Hideshima
Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.
Kenneth C
KC
Anderson
D004359:Drug Therapy, Combination; D057890:Epigenomics / Q000379:methods; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000188:drug therapy*; D061988:Proteasome Inhibitors / Q000627:therapeutic use; D057170:Translational Research, Biomedical
D056572:Histone Deacetylase Inhibitors; D007155:Immunologic Factors; D061988:Proteasome Inhibitors
HDAC inhibitor; Histone deacetylase (HDAC); Immunomodulatory drugs; Multiple myeloma; Proteasome inhibitor