Phosphoproteome and gene expression profiling of ALK inhibition in neuroblastoma cells lines reveals conserved oncogenic pathways

Neuroblastoma is a neural crest-derived embryonal tumor or the postganglionic sympathetic nervous system. Neuroblastomas show heterogeneous biologic and clinical features and , whereas a subset may undergo spontaneous differentiation or regression with little or no therapy, the majorities are difficult to cure with current modalities. The origin of these tumours remains unknown in most cases, although a number of familial cases have been associated with mutations of the ALK gene. In this study we established both phosphoproteomic and gene expression profiles of ALK activity in neuroblastoma cells exposed to first and third generation ALK TKIs, to identify the underlying molecular mechanisms and identify relevant biomarkers, signaling networks, and new therapeutic targets.