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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Overexpression of mTOR and p(240-244)S6 in IDH1 Wild-Type Human Glioblastomas Is Predictive of Low Survival

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Machado, Luis Eduardo [1] ; Alvarenga, Arthur William [1] ; da Silva, Fernanda Ferreira [1] ; Roffe, Martin [1] ; Begnami, Maria Dirlei [2] ; Bleggi Torres, Luis Fernando [3] ; da Cunha, Isabela Werneck [2] ; Martins, Vilma Regina [1] ; Maroso Hajj, Glaucia Noeli [1]
Total Authors: 9
[1] Natl Inst Sci & Technol Oncogen, AC Camargo Canc Ctr, Int Res Ctr, Sao Paulo - Brazil
[2] Natl Inst Sci & Technol Oncogen, AC Camargo Canc Ctr, Dept Pathol, Sao Paulo - Brazil
[3] Inst Pele Pequeno Principe Res Pediat Canc, Curitiba, Parana - Brazil
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY; v. 66, n. 6, p. 403-414, JUN 2018.
Web of Science Citations: 4

PI3K/Akt/mTOR pathway activation is a hallmark of high-grade gliomas, which prompted clinical trials for the use of PI3K and mTOR inhibitors. However, the poor results in the original trials suggested that better patient profiling was needed for such drugs. Thus, accurate and reproducible monitoring of mTOR complexes can lead to improved therapeutic strategies. In this work, we evaluated the expression and phosphorylation of mTOR, RAPTOR, and rpS6 in 195 human astrocytomas and 30 normal brain tissue samples. The expression of mTOR increased in glioblastomas, whereas mTOR phosphorylation, expression of RAPTOR, and expression and phosphorylation of rpS6 were similar between grades. Interestingly, the overexpression of total and phosphorylated mTOR as well as phosphorylated rpS6 (residues 240-244) were associated with wild-type IDH1 only glioblastomas. The expression and phosphorylation of mTOR and phosphorylation of rpS6 at residues 240-244 were associated with a worse prognosis in glioblastomas. Our results suggest that mTOR and rpS6 could be used as markers of overactivation of the PI3K-mTOR pathway and are predictive factors for overall survival in glioblastomas. Our study thus suggests that patients who harbor IDH1 wild-type glioblastomas might have increased benefit from targeted therapy against mTOR. (AU)

FAPESP's process: 15/15451-3 - Study on the Regulation and Function of the RSK Family in Glioblastomas
Grantee:Martín Roffé
Support type: Regular Research Grants
FAPESP's process: 14/15550-9 - Translational control in cancer
Grantee:Glaucia Noeli Maroso Hajj
Support type: Regular Research Grants