Targeting phosphoinositide 3-kinases and histone deacetylases in multiple myeloma

Background: Multiple myeloma (MM) is a type of hematological malignancy affecting the functions of plasma cells. The treatment of MM patients has changed dramatically with the use of new agents. However, unfortunately, it is still incurable. Therefore, a new approach for treating MM is still needed to improve patient outcomes.

Methods: Because the histone deacetylase (HDAC) and phosphoinositide 3-kinase (PI3K) pathway is a key signal in cancer cell biology, we investigated whether dual HDAC and PI3K inhibitors could suppress the myeloma cells.

Results: Gene expression of HDACs is high in myeloma cells. CUDC-907, a dual inhibitor of PI3K and HDAC, inhibits HDAC activity. Akt activity and expression of BCL-XL, MCL-1, and NF-κB p65 were reduced by CUDC-907 in a dose-dependent manner. The number of apoptotic and caspase 3/7-positive cells also increased in the myeloma cells. Combined treatment of myeloma cells with carfilzomib and CUDC-907 increased cytotoxicity compared to that observed with each drug alone.

Conclusions: Data from this study suggested that the administration of CUDC-907 might be a powerful strategy against myeloma cells, to enhance the cytotoxic effects of proteasome inhibitors.

Related Products

Cat.No.	Product Name	Information
S2759	Fimepinostat (CUDC-907)	CUDC-907 is a dual PI3K and HDAC inhibitor for PI3Kα and HDAC1/2/3/10 with IC50 of 19 nM and 1.7 nM/5 nM/1.8 nM/2.8 nM, respectively. CUDC-907 induces cell cycle arrest and apoptosis in breast cancer cells. Phase 1.

Related Targets

HDAC PI3K Apoptosis related