Fig. 9

Proposed mechanism of HDAC, Akt, and PI3K inhibition in MM cells. Lenalidomide increases p-GSK-3 levels, which functions to stabilize c-Myc and enhance MM cell survival, when CRBN expression is reduced. HDAC inhibitor treatment downregulates IKZF1/3, thereby inducing c-Myc downregulation and MICA upregulation. PI3K or Akt inhibitors downregulate p-GSK-3 and c-Myc expression in MM cells. HDAC inhibition also downregulates p-GSK-3. CUDC-907 has the ability to enhance MICA and suppress c-Myc. CUDC-907 is a promising drug that has the advantages of dual HDAC and Akt inhibition