Erlotinib resistance in mouse models of epidermal growth factor receptor-induced lung adenocarcinoma Journal Article
| Authors: | Politi, K.; Fan, P. D.; Shen, R.; Zakowski, M.; Varmus, H. |
| Article Title: | Erlotinib resistance in mouse models of epidermal growth factor receptor-induced lung adenocarcinoma |
| Abstract: | Seventy-five percent of lung adenocarcinomas with epidermal growth factor receptor (EGFR) mutations respond to treatment with the tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib; however, drug-resistant tumors eventually emerge. In 60% of cases, resistant tumors carry a secondary mutation in EGFR (T790M), amplification of MET, or both. Here, we describe the establishment of erlotinib resistance in lung tumors, which were induced by mutant EGFR, in transgenic mice after multiple cycles of drug treatment; we detect the T790M mutation in five out of 24 tumors or Met amplification in one out of 11 tumors in these mice. This preclinical mouse model, therefore, recapitulates the molecular changes responsible for resistance to TKIs in human tumors and holds promise for the discovery of additional mechanisms of drug resistance in lung cancer. |
| Keywords: | signal transduction; genetics; mutation; erlotinib; adenocarcinoma; cell proliferation; mouse; animal; metabolism; animals; mice; gene amplification; lung neoplasms; epidermal growth factor receptor; receptor, epidermal growth factor; drug effect; drug resistance; pathology; drug resistance, neoplasm; transgenic mouse; mice, transgenic; disease model; lung tumor; transgene; disease models, animal; quinazolines; quinazoline derivative; transgenes; scatter factor receptor; proto-oncogene proteins c-met |
| Journal Title: | Disease Models & Mechanisms |
| Volume: | 3 |
| Issue: | 1 |
| ISSN: | 1754-8403 |
| Publisher: | Company of Biologists |
| Date Published: | 2010-01-01 |
| Start Page: | 111 |
| End Page: | 119 |
| Language: | English |
| PUBMED: | 20007486 |
| PROVIDER: | scopus |
| PMCID: | PMC2806903 |
| DOI: | 10.1242/dmm.003681 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 20 April 2011" - "Source: Scopus" |
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