Inhibition of Cyclin Dependent Kinases Overcomes MYC-Driven Secondary Resistance to Everolimus in Digestive NETs

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Introduction: Dysregulation of the mTOR pathway in digestive neuroendocrine tumours (d-NETs) led to the introduction of Everolimus (EVE) as treatment. EVE significantly increases PFS, but most patients acquire resistance, due to activation of feedback loops.

Aim(s): To identify key molecular pathways involved in EVE resistance acquisition.

Materials and methods: BON-1 and BON-1 EVE resistant (RR) cells, mimicking the clinical scenario of primary sensitivity and acquired resistance, were investigated by RNA-seq with validation by RT-qPCR on RNA of 16 ‘baseline’ (before EVE) and 5 ‘progression’ samples (at time of progression after EVE) of d-NETs liver metastases. Cell viability and proliferation were assessed by MTS and cell cycle evaluated by FACS analysis.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Capurso G

Authors: Terracciano F, Capone A, Montori A, Pilozzi E, Arcidiacono P,

Keywords: mTOR, Myc, resistance, pathway, RNA-seq,