Here we’ve found that autophagy happens in MM cells right after rapamycin treatment, correlating with the inhibition of mTOR being an early and low dose response to rapamycin. Since the extent of autophagy increased in a measure and time-dependent fashion without distinctive apoptosis, as assessed by Annexin/PI analysis, we suggest that rapamycins cytotoxic effect on MM cells is principally mediated via autophagy in the place of apoptosis. Since activated Akt has been proven to prevent mTOR and suppress autophagy, we increased rapamycin caused autophagy by perifosine inactivation of Akt. Data from a few studies explain that apoptosis and autophagy could be interconnected in a few settings, and even simultaneously regulated by the same trigger leading to different cellular benefits. Akt/mTOR is among the few converging molecular links in both autophagy and apoptosis signaling. Our data suggests that rapamycin induced autophagy in MM cells results in apoptosis when along with perifosine. Nevertheless, neither alternative, nor concomitant inhibition of Carcinoid apoptosis and autophagy recovered MM cell when rapamycin and perifosine were mixed, indicating an even more complex signaling relationship underlying the synergistic effects of the promising anticancer drug combination. To the end, we applied the in silico predictive modeling system based on statistical analysis of cellular systems provided by a systems-biology approach. Multiscale in silico review of the biology of rapamycin and perifosine combined effects on the cyst cell confirmed and complemented our in vitro experimental findings. While mTOR inhibitors including rapamycin analogs CCI 779, RAD001 and AP23573 have shown preclinical promise, as single agents in phase 2 and 3 studies their roles have led to only modest responses. Pre clinical studies of nab rapamycin in colon and breast cancer in in vivo models demonstrated anti tumor activity, Celecoxib 169590-42-5 indicating potential clinical application. Moreover nab rapamycin was well-tolerated overcoming the constraints presented by the poor water solubility of rapamycin. Specifically the binding of water insoluble rapamycin to nanoparticle albumin permits albumin mediated transcytosis of rapamycin by microvessel endothelial cells and the SPARC albumin discussion may further increase accumulation of albumin bound drug in the tumefaction. As the position of SPARC in MM isn’t fully understood, there is evidence that SPARC is upregulated in extramedullary tumefaction growth of MM. Additionally, nab rapamycin recently proven promising information in phase I clinical trials in patients with advanced non hematologic malignances compelling nab rapamycin to be tested by us inside our studies. We examined the effects of nab rapamycin using the Akt inhibitor perifosine in vivo in our MM murine xenograft models, hypothesizing that anti MM therapeutic effects would be increased both by combined inhibition of the Akt/mTOR route and also due to reduce doses and better tolerability of nab rapamycin.