mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors.

Falletta, Simona; Partelli, Stefano; Rubini, Corrado; Nann, Dominik; Doria, Andrea; Marinoni, Ilaria; Polenta, Vanessa; Di Pasquale, Carmelina; Degli Uberti, Ettore; Perren, Aurel; Falconi, Massimo; Zatelli, Maria Chiara (2016). mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors. Endocrine-related cancer, 23(11), pp. 883-891. BioScientifica Ltd. 10.1530/ERC-16-0329

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Medical therapy of pancreatic neuroendocrine tumors (P-NET) may take advantage of Everolimus treatment. However, the extent of therapeutic response cannot be predicted. This study was aimed to identify the possible predictive markers of response to Everolimus in P-NET. We found that Everolimus reduced the cell viability and induced apoptosis in primary cultures of 6 P-NET (P-NET-R), where the proliferative and antiapoptotic effects of IGF1 were blocked by Everolimus. On the contrary, 14 P-NET primary cultures (P-NET-NR) were resistant to Everolimus and IGF1, suggesting an involvement of PI3K/AKT/mTOR pathway in the mechanism of resistance. The response to Everolimus in vitro was associated with an active AKT/mTOR pathway and seemed to be associated with a greater clinical aggressiveness. In addition, a patient sensitive to Everolimus in vitro was sensitive to this drug in vivo also and showed a positive p-AKT immunohistochemistry (IHC) at tissue level. Similarly, a patient resistant to Everolimus treatment after surgery was not sensitive to the drug in vitro and had a negative p-AKT IHC staining. Therefore, present data confirm that P-NET primary cultures may be considered a model for testing medical treatment efficacy and that IHC characterization of p-AKT might help in identifying human P-NET who can benefit from Everolimus treatment. These data encourage conducting a prospective multicenter study involving different groups of P-NET patients treated with Everolimus.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Falletta, Simona; Marinoni, Ilaria and Perren, Aurel

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1351-0088

Publisher:

BioScientifica Ltd.

Language:

English

Submitter:

Aurel Perren

Date Deposited:

21 Dec 2016 13:53

Last Modified:

21 Dec 2016 13:53

Publisher DOI:

10.1530/ERC-16-0329

PubMed ID:

27697900

Uncontrolled Keywords:

Everolimus; IGF1; pancreatic neuroendocrine tumors; predictive markers; primary cultures

BORIS DOI:

10.7892/boris.91973

URI:

https://boris.unibe.ch/id/eprint/91973

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