The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies.
Document Type
Article
Publication Date
2006
Keywords
Adenocarcinoma-Bronchiolo-Alveolar, Animals, Antibodies-Monoclonal, Antineoplastic-Agents, Enzyme-Activation, Exons, Humans, Lung, Lung-Neoplasms, Mice-Transgenic, Mutation, Protein-Structure-Tertiary, Quinazolines, Quinolines, Receptor-Epidermal-Growth-Factor
First Page
485
Last Page
495
JAX Source
Cancer Cell 2006 Jun; 9(6):485-95.
Abstract
To understand 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.
Recommended Citation
Ji H,
Li D,
Chen L,
Mitchell A,
Chirieac LR,
Bronson RT,
Kim W,
Janne PA,
Weissleder R,
et al .
The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell 2006 Jun; 9(6):485-95.