Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR

By M. Neshat, I. Mellinghoff, C. Tran, B. Stiles, G. Thomas, Roseann Petersen, P. Frost, J. Gibbons, Hong Wu, C. Sawyers. Proceedings of the National Academy of Sciences of the United States of America, 2001

1,019 citations recorded by the source corpus.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3b936b60b6a9f81444d2f1e08702021789b89bad

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In Genetics

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Citations in the corpus

• Growing roles for the mTOR pathway. (2005, background): “Interestingly, many cancer cells without PTEN function and, therefore, with hyperactive Akt/PKB signaling are highly sensitive to the anti-proliferative effects of rapamycin [83,84].”
• Defining the role of mTOR in cancer. (2007, background): “Studies in mouse models support this idea showing that the neoplastic phenotypes induced by pten deletion or transgenic activation of AKT are sensitive to rapamycin (Majumder et al., 2004; Neshat et al., 2001; Podsypanina et al., 2001).”
• PI3K/Akt and apoptosis: size matters (2003, background): “…(Wyeth-Ayerst) and RAD001 (Novartis) recapitulates the inhibitory action of TSC1/TSC2 on mTOR activity, and is very efficient at inhibiting growth arrest and inducing apoptosis in PTEN- or p53-deficient cells (Aoki et al., 2001; Neshat et al., 2001; Podsypanina et al., 2001; Shi et al., 2002).”
• Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium (2018, background): “Temsirolimus showed anti-tumor activities toward several preclinical tumor models and in phase I–III trials for advanced renal cell carcinoma and mantle cell lymphoma (Neshat et al., 2001; Yu et al., 2001; Hudes et al., 2007; Ansell et al., 2008).”
• Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. (2002, background): “Rapamycin treatment decreases colony formation by myrPI3K and myrAkt transformed fibroblasts and has been shown to have activity against PTEN-deficient tumors (Hidalgo and Rowinsky, 2000; Aoki et al., 2001; Neshat et al., 2001; Podsypanina et al., 2001).”
• Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression (2004, background): “…of tumors displaying aberrantly high PI3K-dependent signaling, either through constitutive activation of PI3K or Akt or via inactivation of the PI3K antagonist PTEN, display enhanced sensitivity to rapamycin and analogs (Aoki et al., 2001; Neshat et al., 2001; Podsypanina et al., 2001).”
• mTOR signaling in growth control and disease (2012, neutral): “Substantial work in preclinical models of cancer suggested that loss of PTEN or Von Hippel-Lindau (VHL) might represent biomarkers of rapalog sensitivity (Neshat et al., 2001; Thomas et al., 2006).”
• TOR signalling in bugs, brain and brawn (2003, background): “pl?O00633">PTEN )-deficient cancer cells, in which the PI3K pathway is activated owing to the upregulation of the lipid second messenger phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P 3 ), indicate that inhibition of mTOR blocks signalling through the PI3K pathwa”
• Antitumor Activity of Rapamycin in a Phase I Trial for Patients with Recurrent PTEN-Deficient Glioblastoma (2008, background): “Previous work by our group [9] and others [10–15] demonstrated that mutational activation of the phosphatidyl-inositol-3-kinase (PI3K) pathway through loss of PTEN (phosphatase and tensin homolog deleted on Chromosome 10) or activation of the serine/threonine kinase Akt sensitizes tumor cells to the”
• Oncogenic PI3K deregulates transcription and translation (2005, background): “Sensitivity of tumours to rapamycin is also seen in animal model system”
• Regulation of Hypoxia-Inducible Factor 1α Expression and Function by the Mammalian Target of Rapamycin (2002, background): “The evidence supporting a functional linkage between PI 3-kinase and mTOR has been buttressed by observations that PTEN-deficient cells display increased sensitivities to the antiproliferative and anticancer activities of rapamycin (2, 24, 30, 33, 35).”