mTOR pathway in gastroenteropancreatic neuroendocrine tumor (GEP-NETs).
Zanini, Sara; Renzi, Serena; Giovinazzo, Francesco; Bermano, Giovanna
Professor Giovanna Bermano email@example.com
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: https://doi.org/10.3389/fendo.2020.562505
|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|
|Peer Reviewed||Peer Reviewed|
|Keywords||Neuroendocrine tumor; mTOR; Cancer treatment; Target therapy; GEP-NENs; GEP-NETs|
ZANINI 2020 mTOR pathway (VOR)
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