Article: mTOR Pathway in Gastroenteropancreatic Neuroendocrine Tumor (GEP-NETs).
2020 Volume 11, Page(s) 562505
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cell Proliferation/drug effects ; Cell Proliferation/physiology ; Humans ; Intestinal Neoplasms/drug therapy ; Intestinal Neoplasms/genetics ; Intestinal Neoplasms/metabolism ; Neuroendocrine Tumors/drug therapy ; Neuroendocrine Tumors/genetics ; Neuroendocrine Tumors/metabolism ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Randomized Controlled Trials as Topic/methods ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/genetics ; Stomach Neoplasms/metabolism ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism |
| Chemical Substances | Antineoplastic Agents ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) |
| Language | English |
| Publishing date | 2020-11-16 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Meta-Analysis ; Review |
| ZDB-ID | 2592084-4 |
| ISSN | 1664-2392 |
| ISSN | 1664-2392 |
| DOI | 10.3389/fendo.2020.562505 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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