mTOR pathway activation is a favorable prognostic factor in human prostate adenocarcinoma
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Suzan Stelloo1, Joyce Sanders2, Ekaterina Nevedomskaya1, Jeroen de Jong2, Dennis Peters1, Geert J.L.H. van Leenders3, Guido Jenster4, Andries M. Bergman5, Wilbert Zwart1
1Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
2Division of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
3Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center, Rotterdam, The Netherlands
4Department of Urology, Josephine Nefkens Institute, Erasmus Medical Center, Rotterdam, The Netherlands
5Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Andries M. Bergman, email: [email protected]
Wilbert Zwart, email: [email protected]
Keywords: mTOR, PI3K pathway, ERG, prostate cancer, prognosis
Received: September 14, 2015 Accepted: March 28, 2016 Published: April 16, 2016
Prostate cancer patients with localized disease are treated with curative intent. However, the disease will recur in approximately 30% of patients with a high incidence of morbidity and mortality. Prognostic biomarkers are needed to identify patients with high risk of relapse. mTOR pathway activation is reported in prostate cancer, but clinical trials testing efficacy of mTOR inhibitors were unsuccessful. To explain this clinical observation, we studied the expression and prognostic impact of mTOR-S2448 phosphorylation in localized prostate carcinomas. mTOR-S2448 phosphorylation is indicative for an activated mTOR pathway in prostate cancer. Surprisingly, the mTOR signaling pathway is activated specifically in prostate cancer patients with a favorable outcome. Since tumors from poor-outcome patients have low levels of mTOR-S2448 phosphorylation, this may explain why mTOR inhibitors proved unsuccessful in prostate cancer trials.
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