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mTOR pathway in gastroenteropancreatic neuroendocrine tumor (GEP-NETs).

Zanini, Sara; Renzi, Serena; Giovinazzo, Francesco; Bermano, Giovanna


Sara Zanini

Serena Renzi

Francesco Giovinazzo


Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) originate from neuroendocrine cells in the gastrointestinal tract. They are heterogeneous, and though initially considered rare tumors, the incidence of GEP-NENs has increased in the last few decades. Therapeutic approaches for the metastatic disease include surgery, radiological intervention by chemoembolisation, radiofrequency ablation, biological therapy in addition to somatostatin analogs, and PRRT therapy (177Lu-DOTATATE). The PI3K-AKT-mTOR pathway is essential in the regulation of protein translation, cell growth, and metabolism. Evidence suggests that the mTOR pathway is involved in malignant progression and resistance to treatment through over-activation of several mechanisms. PI3K, one of the main downstream of the Akt-mTOR axis, is mainly involved in the neoplastic process. This pathway is frequently deregulated in human tumors, making it a central target in the development of new anti-cancer treatments. Recent molecular studies identify potential targets within the PI3K/Akt/mTOR pathway in GEP-NENs. However, the use of target therapy has been known to lead to resistance due to several mechanisms such as feedback activation of alternative pathways, inactivation of protein kinases, and deregulation of the downstream mTOR components. Therefore, the specific role of targeted drugs for the management of GEP-NENs is yet to be well-defined. The variable clinical presentation of advanced neuroendocrine tumors is a significant challenge for designing studies. This review aims to highlight the role of the PI3K/Akt/mTOR pathway in the development of neuroendocrine tumors and further specify its potential as a therapeutic target in advanced stages.


ZANINI, S., RENZI, S., GIOVINAZZO, F. and BERMANO, G. 2020. mTOR pathway in gastroenteropancreatic neuroendocrine tumor (GEP-NETs). Frontiers in endocrinology [online], 11, article ID 562505. Available from:

Journal Article Type Article
Acceptance Date Sep 7, 2020
Online Publication Date Nov 16, 2020
Publication Date Dec 31, 2020
Deposit Date Dec 11, 2020
Publicly Available Date Dec 11, 2020
Journal Frontiers in endocrinology
Electronic ISSN 1664-2392
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 11
Article Number 562505
Keywords Neuroendocrine tumor; mTOR; Cancer treatment; Target therapy; GEP-NENs; GEP-NETs
Public URL


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