Rapamycin and its analogues have significant antiproliferative action against a variety of tumors. However, sensitivity to rapamycin is reduced by Akt activation that results from the ablative effects of rapamycin on a p70 S6K-induced negative feedback loop that blunts phosphoinositide 3-kinase (PI3K)-mediated support for Akt activity. Thus, sensitivity to rapamycin might be increased by imposi...

RAFT1/FRAP/mTOR is a key regulator of cell growth and division and the mammalian target of rapamycin, an immunosuppressive and anticancer drug. Rapamycin deprivation and nutrient deprivation have similar effects on the activity of S6 kinase 1 (S6K1) and 4E-BP1, two downstream effectors of RAFT1, but the relationship between nutrient- and rapamycin-sensitive pathways is unknown. Using transcript...

The molecular target of rapamycin (mTOR) is up-regulated in glioblastoma (GBM) and this is associated with the rate of cell growth, stem cell proliferation and disease relapse. Rapamycin is a powerful mTOR inhibitor and strong autophagy inducer. Previous studies analyzed the effects of rapamycin in GBM cell lines. However, to our knowledge, no experiment was carried out to evaluate the effects ...

Rapamycin is a potent cytostatic agent that arrests cells in the G1 phase of the cell cycle. The relationships between cellular sensitivity to rapamycin, drug accumulation, expression of mammalian target of rapamycin (mTOR), and inhibition of growth factor activation of ribosomal p70S6 kinase (p70(S6k)) and dephosphorylation of pH acid stable protein I (eukaryotic initiation factor 4E binding p...

The inhibition of the mammalian target of rapamycin (mTOR) signaling pathway promotes the initiation of autophagy, and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) is well known to induce autophagy. Autophagy is a self-defense mechanism of cancer cells that are subjected to antitumor agents, and blocking autophagy can trigger apoptosis. In the ...

BACKGROUND Signaling through the mTOR pathway contributes to growth, progression and chemoresistance of several cancers. Accordingly, inhibitors have been developed as potentially valuable therapeutics. Their optimal development requires consideration of dose, regimen, biomarkers and a rationale for their use in combination with other agents. Using the infrastructure of the Comparative Oncology...

Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR) kinase. The resulting ternary complex has been used to conditionally perturb protein function, and one such method involves perturbation of a protein of interest through its m...

We present a case of post-transplantation Kaposi's sarcoma (KS) successfully treated by conversion to rapamycin. Clinical and histological resolution was observed within 6 months of commencing rapamycin. Also, vascular endothelial growth factor (VEGF) staining in the biopsy samples resolved following rapamycin therapy. Interestingly there was no expansion in cytotoxic T-lymphocyte (CTL) subsets...

Themammalian targetof rapamycin (mTOR)kinase integratescues fromnutrientsandgrowth factors, acting as a nexus point for cellular signals to control growth,metabolism, and longevity. Deregulation ofeitherofmTOR’s twocomplexes,mTORC1ormTORC2, leads todiseasesofmetabolism, including cancer and diabetes. In this issue’s Select, insights into the extent of mTOR’s oncogenic capabilities come to light...