Dual Inhibitor of PI3K and HDAC Under Study in Multiple Myeloma
Posted: Monday, May 24, 2021
Although new therapies have improved patient outcomes for multiple myeloma, the disease remains incurable, and new approaches continue to be under study. The histone deacetylase (HDAC) and phosphoinositide 3-kinase (PI3K) pathways are key signals in cancer cell biology. Thus, Seiichi Okabe, MD, PhD, of Tokyo Medical University, and colleagues reported that CUDC-907, a dual inhibitor of HDAC and PI3K, may prove to be an effective way to enhance the cytotoxic effects of proteasome inhibitors in patients with myeloma. The study was published in Experimental Hematology & Oncology.
“The use of combination therapy focused on carfilzomib and CUDC-907 may be a potentially good therapeutic strategy to treat relapsed [or] refractory myeloma,” the researchers concluded.
Using multiple myeloma cell lines, the research team investigated whether the dual inhibition of HDAC and PI3K in the presence of proteasome inhibitors reduced the survival and growth of cancer cells. Cells were treated with CUDC-907 alone or in combination with carfilzomib for 72 hours.
CUDC-907 appeared to inhibit HDAC activity and the proliferation of myeloma cells. The researchers noted a reduced expression and Akt activity of BCL-XL, MCL-1, and NF-κB p65 in a dose-dependent manner. The immunoblot analysis also demonstrated reduced BCL-XL and MCL-1 expression, suggesting the dual inhibitor induced death of myeloma cells in vitro. In the multiple myeloma cells, the researchers observed an increase in apoptotic and caspase 3/7–positive cells. Myeloma cells that were treated with carfilzomib plus CUDC-907 showed increased cytotoxicity compared with each drug alone.
Disclosure: The study authors reported no conflicts of interest.