Combination of mTOR inhibitors and IMiD compounds might overcome resistance to IMiD compounds. (A) IMiD compounds inhibit the translation of C/EBPβ by down-regulation of eIF4E protein. Rapamycin targets the mTOR complex by inhibiting 4EBP1 phosphorylation, resulting in sequestering of eIF4E. This blocks the assembly of the translational complex and leads to decreased C/EBPβ translation. (B) MM.1S cells were incubated with rapamycin or DMSO 0.01% as control for 2 days. Cells were lysed, and lysates were analyzed for both total-and phospho-4EBP1 as well as for eIF4E by Western blot. β-actin expression was probed for loading control. (C) RPMI 8226 cells (3 × 10⁴) were cultured with rapamycin or pomalidomide alone or in combination for 2 days. DMSO 0.01% treatment was used as a control. DNA synthesis was measured by ³H-thymidine incorporation. Results are shown as triplicates of mean ± SD.