Identifying and Targeting ROS1 Gene Fusions in Non–Small Cell Lung Cancer

摘要: Purpose: Oncogenic gene fusions involving the 3′ region of ROS1 kinase have been identified in various human cancers. In this study, we sought to characterize fusion genes non–small cell lung cancer (NSCLC) and establish proteins as drug targets. Experimental Design: An NSCLC tissue microarray (TMA) panel containing 447 samples was screened for rearrangement by FISH. This assay also used screen patients with NSCLC. positive samples, identity partner determined through inverse PCR reverse transcriptase PCR. addition, clinical efficacy inhibition assessed treating a ROS1-positive patient crizotinib. The HCC78 line, which expresses SLC34A2–ROS1 fusion, treated inhibitors that activity against ROS1. effects on proliferation, cell-cycle progression, signaling pathways were analyzed MTS assay, flow cytometry, Western blotting. Results: TMA panel, 5 428 (1.2%) evaluable found be rearrangement. 1 48 tested rearrangement, showed tumor shrinkage upon treatment one sample displayed expression recently SDC4–ROS1 whereas two expressed CD74–ROS1 others fusion. cells, antiproliferative downregulated are critical growth survival. Conclusions: may an effective strategy subset whose tumors express genes. Clin Cancer Res; 18(17); 4570–9. ©2012 AACR .