Preclinical Antimyeloma Activity of EDO-S101

e218 were substantially minimized after the heat treatment. The heat treatment also suppressed the clonogenic or self-renewal capacity of these MM cells as determined by in vitro colony formation and in vivo tumor formation in SCID mice, suggesting targeting MM progenitors. Further, the Pim inhibitor SMI16a also reduced the SP sizes and the ability of colony formation in RPMI8226 and KMS11 cells. Interestingly, the Pim inhibition in combination with heat treatment enhanced the induction of CHOP, a suicide mediator, while further reducing the protein levels of IRF4 and c-Myc to facilitate MM cell death. These results collectively demonstrated that hyperthermia is able to impair clonogenic drug-resistant fractions of MM cells, which may be augmented in combination with ER stress inducers, such as bortezomib, as well as Pim inhibition. We are now developing superparamagnetic mesoporous nanoparticles, which are able to deliver tumor-selective hyperthermia and drug release. A new strategy with tumor-selective hyperthermia and drug release warrants further study especially in the setting of drugresistant extramedullary plasmacytomas.