Author/Authors :
Klarisa Rikova، نويسنده , , Ailan Guo، نويسنده , , Qingfu Zeng، نويسنده , , Anthony Possemato، نويسنده , , Jian Yu، نويسنده , , Herbert Haack، نويسنده , , Julie Nardone، نويسنده , , Kimberly Lee، نويسنده , , Cynthia Reeves، نويسنده , , Yu Li، نويسنده , , Yerong Hu، نويسنده , , Zhiping Tan، نويسنده , , Matthew Stokes، نويسنده , , Laura Sullivan-Green، نويسنده , , Jeffrey Mitchell، نويسنده , , Randy Wetzel، نويسنده , , Joan MacNeill، نويسنده , , Jian Min Ren، نويسنده , , Jin Yuan، نويسنده , , Corey E. Bakalarski، نويسنده , , et al.، نويسنده ,
Abstract :
Despite the success of tyrosine kinase-based cancer therapeutics, for most solid tumors the tyrosine kinases that drive disease remain unknown, limiting our ability to identify drug targets and predict response. Here we present the first large-scale survey of tyrosine kinase activity in lung cancer. Using a phosphoproteomic approach, we characterize tyrosine kinase signaling across 41 non-small cell lung cancer (NSCLC) cell lines and over 150 NSCLC tumors. Profiles of phosphotyrosine signaling are generated and analyzed to identify known oncogenic kinases such as EGFR and c-Met as well as novel ALK and ROS fusion proteins. Other activated tyrosine kinases such as PDGFRα and DDR1 not previously implicated in the genesis of NSCLC are also identified. By focusing on activated cell circuitry, the approach outlined here provides insight into cancer biology not available at the chromosomal and transcriptional levels and can be applied broadly across all human cancers.
