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Gelsomino F, Casadei-Gardini A, Caputo F, et al. mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus. Cancers (Basel). 2020;12(5)doi: 10.3390/cancers12051201.
Gelsomino, F., Casadei-Gardini, A., Caputo, F., Rossi, G., Bertolini, F., Petrachi, T., Spallanzani, A., Pettorelli, E., Kaleci, S., & Luppi, G. (2020). mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus. Cancers, 12(5), . https://doi.org/10.3390/cancers12051201
Gelsomino, Fabio, et al. "mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus." Cancers vol. 12,5 (2020). doi: https://doi.org/10.3390/cancers12051201
Gelsomino F, Casadei-Gardini A, Caputo F, Rossi G, Bertolini F, Petrachi T, Spallanzani A, Pettorelli E, Kaleci S, Luppi G. mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus. Cancers (Basel). 2020 May 10;12(5). doi: 10.3390/cancers12051201. PMID: 32397669; PMCID: PMC7281483.
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Cancers (Basel). 2020 May 10;12(5). doi: 10.3390/cancers12051201.

mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus.

Cancers

Fabio Gelsomino, Andrea Casadei-Gardini, Francesco Caputo, Giulio Rossi, Federica Bertolini, Tiziana Petrachi, Andrea Spallanzani, Elisa Pettorelli, Shaniko Kaleci, Gabriele Luppi

Affiliations

  1. Department of Oncology and Hematology, University Hospital of Modena, 41124 Modena, Italy.
  2. Pathology Unit, Azienda USL della Romagna, 48121 Ravenna, Italy.
  3. Scientific and Technological Park of Medicine "Mario Veronesi", 41037 Mirandola (MO), Italy.
  4. Department of Diagnostic Medicine, Clinical and Public Health, University Hospital of Modena, 41124 Modena, Italy.

PMID: 32397669 PMCID: PMC7281483 DOI: 10.3390/cancers12051201

Abstract

BACKGROUND: Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phosphorilated (p)-mTOR and p70S6-kinase (S6K), a downstream effector of mTOR, correlates with the outcome of patients with NET that were treated with Eve.

METHODS: Tissue specimens that were derived from NETs treated with Eve at our Institution were examined for the expression levels of p-mTOR and p-S6K by immunohistochemistry. Response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed in two groups: p-mTOR/p-S6K positive (group 1) and p-mTOR/p-S6K negative (group 2). Univariate and multivariate Cox regression analysis were performed.

RESULTS: Twenty-four patients with advanced NETs that were treated with Eve were included in the analysis. Eight out 24 (33.3%) patients were both p-mTOR and p-S6K positive. A better median PFS and OS in group 1 (18.2 and 39.9 months) as compared to group 2 (13 and 32.4 months) was depicted, with a toxicity profile that was comparable with data literature.

CONCLUSIONS: Our study suggests that the activation of mTOR pathway can predict better outcomes in patients with NET treated with Eve. However, these results warrant further confirmation in a prospective setting.

Keywords: everolimus; mTOR inhibitor; neuroendocrine tumors; prognosis; survival prediction

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