PhD defence T.A.L. (Timon) Vandamme

Pancreatic neuroendocrine neoplasms (pNENs) comprise only 1-2% of all pancreatic neoplasms, with an incidence of about 0.48 per 100,000 person years. Recent advances in next-generation sequencing (NGS) has led to a better understanding of the genetic constitution of pNENs, uncovering the role of the phosphoinositide3-kinase (PI3K)/protein kinase B (Akt)/mTOR signalling in these tumors. Surgical resection is the primary treatment in locoregional pNENs, and the only curative treatment option. However, more than 50% of cases present with unresectable disease at time of diagnosis. For these advanced pNENs, the mTOR-inhibitor everolimus, a so-called rapalog, has demonstrated to improve progression-free survival. However, primary and acquired resistance to everolimus, may limit its efficacy as single treatment modality. In acquired resistance, patients who initially respond to everolimus, later relapse and develop resistance, whereas in primary resistance, patients do not respond at all. To allow in vitro study of pNEN, the BON-1 and QGP-1 human cell lines have been developed. In this thesis, we characterize the genetic make-up of both cell lines and compare it to patient samples. In addition, we establish a model for acquired everolimus resistance and use this to uncover everolimus resistance mechanisms.

Due to corona, the PhD defences do not take place publicly in the usual way in the Senate Hall or in the Professor Andries Querido Room. The candidates will defend their dissertation either in a small group or online.