data shows that mutual suppression of the PI3K mTOR pathway by rapamycin and perifosine mix triggers synergistic Fostamatinib 1025687-58-4 MM cell cytotoxicity, providing the rationale for clinical trials in patients with relapsed / refractory MM. Multiple myeloma is a bone-marrow cancer influenced by the relationship between clonal plasma cells and the BM microenvironment. Among the major pathways mediating cytokine induced MM cell growth and survival, PI3K/Akt/mTOR kinase stream represents a cardinal role in cell proliferation, survival and growth of drug resistance. Cytokine induced activation of Akt leads to various down stream anti apoptotic consequences via BAD and forkhead transcription aspect phosphorylation and inhibition of the catalytic subunit of caspase 9. Besides its direct anti-apoptotic results, g Akt promotes development and survival via phosphorylation of glycogen synthase kinase 3B and mammalian target of rapamycin. Moreover, Akt induced activation of mTOR, helps mRNA translation through the activation of P70S6 kinase and the inhibition Cellular differentiation of 4EBP1, a translational repressor of mRNAs. Therefore Akt which is constitutively activated in MM patient cells and correlates with poor prognosis and advanced stage, represents a target for novel therapeutics. Pinpointing mTOR as a vital kinase downstream of Akt generated the prediction that rapamycin, an universal inhibitor of mTORC1 dependent S6K1 phosphorylation could be useful in the treatment of MM. In vitro and in vivo preclinical studies have demonstrated anti MM activity of rapamycin and its analogs. When used as individual agents have shown only moderate efficacy in clinical trials, causing attempts to establish components main rapamycin weight first generation mTOR inhibitors. A growing human body of evidence supports the hypothesis that resistance to rapamycin results order Cabozantinib from a powerful positive feedback loop from mTOR/S6K1 to Akt, leading to Akt activation. Indeed immunohistochemical analysis of paired tissue biopsies, before and after treatment with rapamycin types, revealed that low responders frequently develop increased p Akt, supporting the view that increased intra tumoral phosphorylation of Akt mediates rapamycin opposition. The low response rate seen in many cyst types to rapamycin types resulted in two strategies to overcome rapamycin resistance. First, the execution of nano compound albumin bound technology to increase rapamycin supply to tumefaction tissue. 2nd, combination techniques such as rapamycin with lenalidomide with the capacity to overcome the protective effects of growth factors in the tumor milieu have been in use. Given that PI3K/Akt activity is induced by mTOR inhibitors in MM cells, we’ve examined the utility of adding an Akt inhibitor to over come mTOR resistance and have also taken the benefit of nano compound technology with nab rapamycin.