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June 7th

• Drug's Epilepsy-preve ntion Effect May Be Widely Applicable

May 27th

• Rapamycin, Autophagy, and Longevity
• Autophagy is required for extension of yeast chron...[Autop hagy. 2009] - PubMed Result

May 3rd

• The NF1 tumor suppressor critically regulates TSC2 and mTOR: Loss-of-functi on mutations in the NF1 tumor suppressor gene underlie the familial cancer syndrome neurofibromato sis type I (NF1). The NF1-encoded protein, neurofibromin, functions as a Ras-GTPase activating protein (RasGAP). Deregulation of Ras is thought to contribute to NF1 development. The critical effector pathways involved in disease pathogenesis are still unknown. mTOR pathway is tightly regulated by neurofibromin. mTOR is constitutively activated in both NF1-deficient primary cells and human tumors in the absence of growth factors. This aberrant activation depends on Ras and PI3 kinase, and is mediated by the phosphorylatio n and inactivation of the TSC2-encoded protein tuberin by AKT. Findings identify NF1 tumor suppressor as an indispensable regulator of TSC2 and mTOR. Results also demonstrate that Ras plays a critical role in the activation of mTOR in both normal and tumorigenic settings. Data suggest that rapamycin, or its derivatives, may represent a viable therapy for NF1.

April 18th

• Targeting the mTOR Signaling Network for Cancer Therapy -- Meric-Bernstam and Gonzalez-Angul o, 10.1200/JCO.20 08.20.0766 -- Journal of Clinical Oncology: Rapalogs may be more effective in combination with other anticancer agents, including chemotherapy and targeted therapies. It is increasingly apparent that the mTOR signaling network is quite complex, and rapamycin treatment leads to different signaling responses in different cell types. A better understanding of mTOR signaling, the mechanism of action of rapamycin, and the identification of biomarkers of response will lead to more optimal targeting of this pathway for cancer therapy.
• Blood -- Mammalian target of rapamycin (mTOR) inhibition activates phosphatidylin osit...: The phosphatidylin ositol 3-kinase (PI3K)/Akt and mTORC1 pathways are frequently activated, representing potential therapeutic targets in acute myeloid leukemia (AML).
• An ATP-competitiv e mTOR inhibitor reveals rapamycin-inse nsitive functions of mTORC1 -- Thoreen et al., 10.1074/jbc.M9 00301200 -- Journal of Biological Chemistry: The mTOR kinase is the catalytic subunit of two functionally distinct complexes, mTORC1 and mTORC2, that coordinately promote cell growth, proliferation, and survival. Rapamycin is a potent allosteric mTORC1 inhibitor with clinical applications as an immunosuppress ant and anti-cancer agent. Here, we find that Torin1, a highly potent and selective ATP-competitiv e mTOR inhibitor that directly inhibits both complexes, impairs cell growth and proliferation to a far greater degree than rapamycin.
• mTOR inhibition influences cell viability of medullary thyroid carcinoma primary cultures: Effective medical therapy for persistent/rec urrent medullary thyroid carcinoma (MTC) is not available, yet. Everolimus (RAD001) is a Rapamycin derivative, a potent mTOR pathway inhibitor. RAD001 has been employed in several clinical studies demonstrating antiproliferat ive and apoptotic effects in human tumors, both in vitro and in vivo, also in combination with somatostatin analogs. Results suggest Afinitor might be a useful treatment in combination with octreotide

April 7th

• Loewith Lab

November 19th

• Landes Bioscience - Home
• Rapamycin: an anti-cancer immunosuppress ant? [Crit Rev Oncol Hematol. 2005] - PubMed Result
• Therapeutic potential of target of rapamycin inhib...[Exper t Opin Ther Targets. 2004] - PubMed Result
• Aging and immortality: quasi-programm ed senescence...[ Cell Cycle. 2006] - PubMed Result
• Program-like aging and mitochondria: instead of ra...[J Cell Biochem. 2007] - PubMed Result

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