The targeted drug inhibitor everolimus is one of the few approved therapies for advanced neuroendocrine tumors (NETs), a common type of gut cancer. However, most patients develop a resistance after less than one year. In this project we will investigate the mechanisms of everolimus resistance in two human pancreatic NET cell lines showing stable resistance to everolimus and in an everolimus-resistant tumor grafted in to mice. We will also explore whether the new drug BYL719 can overcame everolimus resistance, as we have already shown in cell lines. The resistance-associated signaling pathway alterations will be investigated in human tumor tissue from patients who have been treated with everolimus in order to find biomarkers of everolimus resistance.

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