mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors
| Autor: | Maria Chiara Zatelli, Corrado Rubini, Andrea Doria, Carmelina Di Pasquale, Massimo Falconi, Aurel Perren, Ilaria Marinoni, Stefano Partelli, Dominik Nann, Vanessa Polenta, Ettore C. degli Uberti, Simona Falletta |
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| Přispěvatelé: | Falletta, Simona, Partelli, Stefano, Rubini, Corrado, Nann, Dominik, Doria, Andrea, Marinoni, Ilaria, Polenta, Vanessa, Di Pasquale, Carmelina, Uberti, Ettore Degli, Perren, Aurel, Falconi, Massimo, Zatelli, Maria Chiara |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Cancer Research Endocrinology Diabetes and Metabolism Predictive marker Neuroendocrine tumors Pharmacology Primary cultures 0302 clinical medicine Endocrinology Tumor Cells Cultured 610 Medicine & health TOR Serine-Threonine Kinases IGF1 Middle Aged Prognosis Diabetes and Metabolism Neuroendocrine Tumors Everolimu Treatment Outcome Oncology 030220 oncology & carcinogenesis Immunohistochemistry Female Signal Transduction medicine.drug Adult Cell Survival Primary Cell Culture Predictive markers NO Young Adult 03 medical and health sciences Pancreatic neuroendocrine tumor In vivo Biomarkers Tumor medicine Humans Everolimus Viability assay Pancreatic neuroendocrine tumors Protein Kinase Inhibitors Protein kinase B PI3K/AKT/mTOR pathway Aged Primary culture Sirolimus business.industry medicine.disease Pancreatic Neoplasms 030104 developmental biology Cancer research 570 Life sciences biology business |
| Zdroj: | Endocrine-Related Cancer. 23:883-891 |
| ISSN: | 1479-6821 1351-0088 |
| DOI: | 10.1530/erc-16-0329 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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