Deacetylase Inhibitors as a Novel Modality in the Treatment of Multiple Myeloma
Richardson PG (1), Moreau P (2), Laubach JP (3), Maglio ME (4), Lonial S (5), San-Miguel J (6).
(1) Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, United States.
(2) University Hospital of Nantes, 1 place Alexis Ricordeau, 44093 - Nantes Cedex 1, France.
(3) Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, United States.
(4) Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, United States.Michelle_Maglio@DFCI.HARVARD.EDU.
(5) Winship Cancer Institute, Emory University, 1365-C Clifton Road, Atlanta, GA, 30322, United States.
(6) Clínica Universidad de Navarra, Universidad de Navarra, CIMA, IDISNA, Av. de Pio XII, 36, 31008 Pamplona, Navarra, Spain.
Deacetylase enzymes remove acetyl groups from histone and nonhistone proteins. Dysregulation of deacetylase activity is a hallmark of malignancy, including multiple myeloma (MM).
Deacetylase inhibitors (DACi) cause epigenetic modification and inhibition of the aggresome pathway, resulting in death of MM cells. Panobinostat, a pan-DACi, has shown significant clinical benefit and is the first DACi approved for the treatment of MM.
It is approved for use in combination with bortezomib and dexamethasone for the treatment of patients with relapsed or relapsed and refractory MM who have received ≥2 prior regimens including bortezomib and an immunomodulatory drug.
Ricolinostat and ACY-241, which selectively inhibit HDAC6 and the aggresome pathway, are currently being studied in combination with dexamethasone and bortezomib or an immunomodulatory drug for the treatment of relapsed and refractory MM.
In this review, we discuss the data from key clinical trials investigating deacetylase inhibitors as novel treatment options for MM.
CITATION Pharmacol Res. 2016 Nov 21. pii: S1043-6618(16)31192-6. doi: 10.1016/j.phrs.2016.11.020