Signaling pathway screening platforms are an efficient approach to identify therapeutic targets in cancers that lack known driver mutations: a case report for a cancer of unknown primary origin

Activation of the AKT pathway in a neuroendocrine tumor of unknown primary origin. a Scheme depicting sample collection and processing for the TARGET clinical trial and the studies performed for the molecular analysis of the tumor specimen TAR007. WBC White Blood Cells, WG Whole Genome, WE Whole Exome. b Whole genome sequencing from the tumor and a patient-derived sample shows extensive copy number variations, including amplifications in 3q and 5p chromosomes. c Phosphokinase arrays from tumor-derived low passage cell cultures show activation of several components of the AKT-mTOR signaling pathway compared to normal primary cells NHBE (normal human bronchial epithelium) and SAEC (small airway epithelial cells). d Phospho-receptor tyrosine kinase (RTK) arrays from TAR007 low passage-derived cell cultures show different RTK activation profiles. e Western blot confirming overexpression of PIK3CA (aka p110α) and RICTOR, as well as hyperactivation of AKT in TAR007-derived cell cultures. GAPDH was used as a loading control. Uncropped blots are available in Figure S