Activation of mTOR in a subgroup of ovarian carcinomas: Correlation with p-eIF-4E and prognosis

Aurelia Noske, Juliane Lena Lindenberg, Silvia Darb-Esfahani, Wilko Weichert, Ann Christin Buckendahl, Annika Röske, Jalid Sehouli, Manfred Dietel, Carsten Denker

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Ovarian carcinoma patients have an extremely poor prognosis; therefore, new molecular therapeutic approaches are urgently needed. The mTOR pathway, which may be targeted by substances such as Rapamycin or RAD001, is emerging as a promising target for anticancer therapy. So far, the expression and prognostic impact of mTOR signalling elements have not been completely studied in ovarian tumors. We analyzed p-mTOR, p-4E-BP1 and p-eIF-4E in 107 human ovarian lesions and observed an overexpression of p-mTOR (47%) and p-eIF-4E (56%) protein in primary ovarian carcinomas as compared to borderline tumors. Phospho-mTOR expression was significantly related to peIF-4E (p≤0.001) and serous histological type (p=0.03). Increased p-4E-BP1 (31%) was associated with poor differentiation (p=0.04) and higher mitotic rate (p=0.004). In univariate analysis, increased expression of p-mTOR and peIF-4E was significantly associated with better overall survival (p=0.003, p=0.029). To connect the expression data with mechanistic studies, a set of 10 ovarian cancer cell lines was used. Expression of p-mTOR was increased in all cancer cell lines as compared to ovarian surface epithelial (HOSE) cells. Rapamycin treatment revealed a reduction of p-mTOR and p-4E-BP1 but increased p-AKT levels. We show for the first time an association of p-mTOR and p-eIF-4E with better overall survival for ovarian cancer patients. The combined results of our in vivo and cell culture studies suggest that a subpopulation of these patients may benefit from mTOR inhibition. The design of future clinical trials should incorporate biomarker testing to determine predictive markers for response to mTOR inhibitors.

Original languageEnglish
Pages (from-to)1409-1417
Number of pages9
JournalOncology Reports
Issue number6
StatePublished - 2008
Externally publishedYes


  • Ovarian cancer
  • Rapamycin
  • p-eiF-4E
  • p-mTOR


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