Temsirolimus

Temsirolimus (CCI-779) inhibited the growth of xenografts derived from both cell lines with greater effects against PC-3 than DU145 tumors. Temsirolimus caused mild myelosuppression. The activity of mitoxantrone or docetaxel was limited, but CCI-779 given between courses of chemotherapy increased growth delay of PC-3 xenografts. High-dose temsirolimus inhibits mTOR signaling through an FKBP12-independent mechanism that leads to profound translational repression. This distinctive high-dose drug effect could be directly related to the antitumor activities of temsirolimus and other rapalogues in human cancer patients. The rapamycin analogue CCI-779 is an important new agent to investigate in the treatment of human brain tumors, particularly PNET/MB. The rapamycin analogue temsirolimus improved performance on four different behavioral tasks and decreased aggregate formation in a mouse model of Huntington disease.