Efficacy of combined inhibition of mTOR and ERK/MAPK pathways in treating a tuberous sclerosis complex cell model

The long and winding road to rational treatment of cancer associated with LKB1/AMPK/TSC/mTORC1 signaling

“…Preclinical studies have demonstrated the ability of rapamycin to inhibit mTORC1 activity and cell growth in murine and human TSC1-or TSC2-deficient cells Onda et al, 2002;Zhang et al, 2003a;Uhlmann et al, 2004;Jozwiak et al, 2009;Mi et al, 2009;Habib et al, 2010;Lee et al, 2010). In vivo, rapamycin treatment reduced the tumor burden and increased survival in TSC-deficient animal models developing renal tumors (Kenerson et al, 2005;Lee et al, 2005Lee et al, , 2006Pollizzi et al, 2009;Woodrum et al, 2010).…”

Avian influenza A virus H5N1 causes autophagy-mediated cell death through suppression of mTOR signaling

“…Wt, p53 À/À , p53 À/À ;Tsc2 À/À , Tsc2 À/À and Pten À/À MEF cell lines have been described previously (Zhang et al, 2003(Zhang et al, , 2007Mi et al, 2009;Ma et al, 2010). All cells were cultured in DMEM with 10% FBS in 5% CO 2 at 37 C. For viral infection, cells were plated and infected with viruses or an equal volume of vehicle the following day at 10 MOI (multiplicity of infection) for indicated times, and then subjected to further study.…”

Expanding therapeutic targets in bladder cancer: the PI3K/Akt/mTOR pathway

“…Various studies have looked at mTOR inhibition in combination with direct Akt (ie perifosine) or PI3K inhibition (ie LY294002), or even through other signaling pathways such as the MAPK/extracellular signal-regulated kinase pathway or epidermal growth factor receptor inhibition. 34,[38][39][40] Studies have found that such combinations result in synergistic effects on cell culture growth, 34 while also giving concern for possible increased benign tissue toxicity because of the pan-interruption of these critical signaling networks. Recent interest has focused on the role of the mTORC2 complex and its potential role in regulating the PI3K/Akt/ mTOR pathway.…”