The mammalian target of rapamycin(mTOR)and its molecular pathways are supposed 
to be activated frequently in human renal cell carcinoma as well as other 
cancers. It has a kinase activity for 40S ribosomal protein kinase and 
eukaryotic translation initiation factor 4E-binding protein 1. These proteins, 
when phosphorylated, promote protein translation and RNA transcription in the 
nutrient-rich condition. mTOR inhibitors such as Temsirolimus (CCI779) and 
Everolimus (RAD001) are effective for suppressing cell growth with inhibiting 
mTOR kinase activity. Rapamycin and its related analogs such as Temsirolimus and 
Everolimus are less toxic for humans compared with other anti-VEGFR inhibitors 
and has been used as an immunosuppressive agent. These agents have an inhibitory 
activity against the mTORC1 complex. Since they do not have inhibitory activity 
against mTORC2 complex, the ability of mTOR inhibition by Temsirolimus is 
supposed to be 40 to 50% of full inhibition in mTOR kinase. Temsirolimus has 
modest anticancer activity against advanced clinical RCC patients with poor 
risk. The objective response rate was only 7%, 26% of patients experienced minor 
responses and another 17% of patients had stable disease that lasted 6 months. 
The median time to tumor progression and median survival for the study patients 
were 5.8 and 15.0 months, respectively. The overall survival of patients treated 
with Temsirolimus alone was statistically longer than in those treated with IFN 
alone in the 626 cases in phase II study. Combinations of mTOR with other anti- 
VEGFR agents were not effective. Vertical therapies of mTOR inhibitor in 
combination with AKT inhibitors, or newly development of stronger mTOR kinase 
which can suppress both mTORC1 and mTORC2 are planned at present.