Expression and Phosphorilation of mTOR Pathway and Antitumor Activity of mTOR Inhibitors in Neuroendocrine Tumors

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Introduction: The mammalian target of rapamycin (mTOR) is a protein kinase involved in the control of cancer cell metabolism, growth and proliferation. The mTOR pathway has attracted broad scientific and clinical interest, particularly in light of the ongoing clinical cancer trials with mTOR inhibitors in pts with neuroendocrine tumors (NETs). To identify the best candidates for treatment with mTOR inhibitors is challenging.

Aim(s): To investigate mTOR pathway in NET cell lines and tumor samples and to correlate mTOR expression and phosphorylation and clinical outcome.

Materials and methods: This study analyzed the expression of phosphorylated mTOR factors, the ribosomal p70S6-kinase (S6K) and the eukaryotic initiation factor 4E-binding protein 1 (4EBP1) in a series of pancreatic NETs. The effects of mTOR inhibitors rapamycin and everolimus in the NCI-H727 cell line (human bronchial carcinoid) were also investigated. Viability was evaluated by MTT assay at three, six, and nine days of treatment with mTOR inhibitors at escalating doses.

Conference: 10th Annual ENETSConcerence (2013)

Presenting Author:

Authors: Sciammarella C, Pivonello C, Sarnataro M, Marotta V, Ramundo V,

Keywords: mTOR pathway, everolimus, pancreatic NET, bronchial carcinoids,