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Unraveling the carcinogenesis and therapy resistance of pancreatic neuroendocrine tumors

Boek - Dissertatie

The general aim of this thesis was to further elucidate the genetic drivers in the oncogenesis of pancreatic neuroendocrine tumors and to unravel the molecular mechanisms that confer everolimus resistance in this cancer. To study this aim, we used multiple approaches to unravel the molecular architecture in this cancer type, including next-generation sequencing methods, drug-treatment cell proliferation assays and bioinformatic algorithms. The genetic basis of pancreatic neuroendocrine tumors has been an evolving field in the last decade. Here, we wanted to investigate the contribution of known pancreatic neuroendocrine oncogenesis driving genes in clinical samples and evaluate whether tumor heterogeneity exists in pancreatic neuroendocrine tumors using a targeted resequencing technique. Everolimus resistance in pancreatic neuroendocrine tumors is a major limitation on the treatment efficacy of this therapeutic. The aim here was to unravel the underlying mechanism that confer resistance and identify novel therapeutic targets in in vitro models using proliferation assays and next-generation sequencing techniques. Through the investigation of the oncogenesis of pancreatic neuroendocrine tumors by means of genetic and other molecular techniques in clinical samples and everolimus-resistant cell lines, we aimed to increase the overall knowledge of this cancer type, unravel the important signaling pathways (and players) and unveil clinically relevant therapeutic targets for overcoming everolimus resistance.
Aantal pagina's: 226
Jaar van publicatie:2020
Trefwoorden:Doctoral thesis
Toegankelijkheid:Open