Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer

By G. Thomas, C. Tran, I. Mellinghoff, Derek S. Welsbie, E. Chan, B. Fueger, J. Czernin, C. Sawyers. Nature Medicine, 2006

640 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/a8640b6b1222fd253b0b3d0058c60641a121e5c1

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Citations in the corpus

Phase 3 trial of everolimus for metastatic renal cell carcinoma (2010, background): “Abnormal functioning of the mTOR pathway may contribute to the pathogenesis of renal cell carcinoma (RCC).(1,2)”
Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK. (2008, background): “Also, Akt phosphorylates FOXO transcription factors to induce their nuclear export, suppressing their proapoptotic function (Tran et al. 2003).”
Digoxin and other cardiac glycosides inhibit HIF-1α synthesis and block tumor growth (2008, neutral): “For example, HIF-1 overexpression identifies patients with kidney cancer that are sensitive to mTOR inhibitors (15).”
The von Hippel–Lindau tumour suppressor protein: O2 sensing and cancer (2008, background): “, and VHL −/− renal carcinoma cells appear to be highly sensitive to mTOR inhibitors in laboratory experiment”
Activation of a metabolic gene regulatory network downstream of mTOR complex 1. (2010, background): “mTORC1 signaling increases HIF1α protein levels by promoting mRNA translation from its 5'UTR (Laughner et al., 2001; Thomas et al., 2006), and we find that this induction requires the inhibitory phosphorylation of 4E-BP1.”
Hypoxia signalling in cancer and approaches to enforce tumour regression (2006, background): “Translation of HIF-1α has been found to be particularly sensitive to growth factors that activate mTO”
Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer (2009, background): “In renal cell carcinoma, loss of the von Hippel–Lindau tumour suppressor ( VHL ) that normally inhibits HIF1A (hypoxia-inducible factor 1, α subunit) leads to enhanced vascularization and sensitizes cancer cells to the mTOR inhibitor CCI-779 (Ref”
Defining the Role of Hypoxia-Inducible Factor 1 in Cancer Biology and Therapeutics (2009, neutral): “, 2001) and the mTOR inhibitors rapamycin, temsirolimus/CCI-779 and everolimus/RAD-001 (Laughner et al., 2001; Majumder et al., 2004; Thomas et al., 2006), which all function by inhibiting mTOR-dependent translation of HIF-1a mRNA into protein (Laughner et al.”
mTOR: from growth signal integration to cancer, diabetes and ageing (2010, background): “In addition, mTORC1 potently promotes angiogenesis by regulating hypoxia-inducible factor 1α (HIF1α); thus, mTORC1 signalling favours the growth of tumours by supplying them with nutrients and oxyge”
The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review) (2017, neutral): “…effectors and consequently increases the synthesis of cell cycle proteins such as hypoxia-inducible factor-1 (HIF-1) (cyclin D and HIF-1 α ) which in turn stimulates vascular endothelial growth factor (VEGF) (113,114). mTOR is particularly active in renal cancer by promoting angiogenesis (115,116).”
mTOR and cancer: insights into a complex relationship (2006, background): “By inhibiting the mTORC1-dependent translation and activity of HIF1α (hypoxia-induced factor 1α”
The impact of O2 availability on human cancer (2008, background): “Renal carcinoma cells, which often exhibit mutations in VHL , have also been shown to downregulate HIF1α expression in response to mTOR inhibitio”