Author/Authors :
Ji، نويسنده , , Hongbin and Li، نويسنده , , Danan and Chen، نويسنده , , Liang and Shimamura، نويسنده , , Takeshi and Kobayashi، نويسنده , , Susumu and McNamara، نويسنده , , Kate and Mahmood، نويسنده , , Umar and Mitchell، نويسنده , , Albert Y. Sun، نويسنده , , Yangping and Al-Hashem، نويسنده , , Ruqayyah and Chirieac، نويسنده , , Lucian R. and Padera، نويسنده , , Robert and Bronson، نويسنده , , Roderick T. and Kim، نويسنده , , William and Jنnne، نويسنده , , Pasi A. and Shapiro، نويسنده , , Geoffrey I. and Tenen، نويسنده , , Daniel and Johnson، نويسنده , , Bruce E. and Weissleder، نويسنده , , Ralph and Sharpless، نويسنده , , Norman E. and Wong، نويسنده , , Kwok-Kin، نويسنده ,
Abstract :
Summary
erstand the role of human epidermal growth factor receptor (hEGFR) kinase domain mutations in lung tumorigenesis and response to EGFR-targeted therapies, we generated bitransgenic mice with inducible expression in type II pneumocytes of two common hEGFR mutants seen in human lung cancer. Both bitransgenic lines developed lung adenocarcinoma after sustained hEGFR mutant expression, confirming their oncogenic potential. Maintenance of these lung tumors was dependent on continued expression of the EGFR mutants. Treatment with small molecule inhibitors (erlotinib or HKI-272) as well as prolonged treatment with a humanized anti-hEGFR antibody (cetuximab) led to dramatic tumor regression. These data suggest that persistent EGFR signaling is required for tumor maintenance in human lung adenocarcinomas expressing EGFR mutants.
