Differential Signalling Pathways Drive Therapeutic Resistance in Neuroendocrine Tumors Abstract #2091

Introduction: Most of the current therapeutic strategies used for neuroendocrine tumors (NETs) are insufficient due to poor knowledge of these tumours. Despite showing differentiated features, NETs often exhibit therapeutic resistance to common treatments similarly to other cancers. Although signalling abnormalities have been reported, molecular mechanisms responsible for this resistance phenomenon are yet to be understood.
Aim(s): We aim at identifying signalling partners responsible of acquired resistance to treatments in order to develop novel therapeutic strategies based on drug combinations to prevent resistance occurence.
Materials and methods: We engineered NETs cell lines, BON-1 and QGP-1, resistant to current leading treatments, Oxaliplatin and Everolimus. We used microarray-based kinomics to obtain highthroughput kinase activity profiles from drug sensitive vs resistant cells and identify "hit" kinases hyperactivated in resistant cells. We then tested resistant cells sensitivity to inhibitors targeting these "hit" kinases.
Conference: 15th Annual ENETS conference (2018)
Category: Basic Science - Signaling pathways, receptors, biomarkers
Presenting Author: Dr David Romano

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