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Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Ji, Hongbin Zhao, Xiaojun Yuza, Yuki Shimamura, Takeshi Li, Danan Protopopov, Alexei Jung, Boonim L. McNamara, Kate L. Xia, Huili Glatt, Karen A. Thomas, Roman K. Sasaki, Hidefumi Horner, James W. Eck, Michael Mitchell, Albert Sun, Yangping Al-Hashem, Ruqayyah Bronson, Roderick Terry Sridhar K. Rabindran Discafani, Carolyn M. Maher, Elizabeth M. Shapiro, Geoffrey I. Meyerson, Matthew Wong, Kwok-Kin |
| Copyright Year | 2006 |
| Abstract | The tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) have shown anti-tumor activity in the treatment of non-small cell lung cancer (NSCLC). Dramatic and durable responses have occurred in NSCLC tumors with mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). In contrast, these inhibitors have shown limited efficacy in glioblastoma, where a distinct EGFR mutation, the variant III (vIII) in-frame deletion of exons 2-7, is commonly found. In this study, we determined that EGFRvIII mutation was present in 5% (3/56) of analyzed human lung squamous cell carcinoma (SCC) but was not present in human lung adenocarcinoma (0/123). We analyzed the role of the EGFRvIII mutation in lung tumorigenesis and its response to tyrosine kinase inhibition. Tissue-specific expression of EGFRvIII in the murine lung led to the development of NSCLC. Most importantly, these lung tumors depend on EGFRvIII expression for maintenance. Treatment with an irreversible EGFR inhibitor, HKI-272, dramatically reduced the size of these EGFRvIII-driven murine tumors in 1 week. Similarly, Ba/F3 cells transformed with the EGFRvIII mutant were relatively resistant to gefitinib and erlotinib in vitro but proved sensitive to HKI-272. These findings suggest a therapeutic strategy for cancers harboring the EGFRvIII mutation. |
| Starting Page | 510 |
| Ending Page | 512 |
| Page Count | 3 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pnas.org/content/103/20/7817.full.pdf |
| PubMed reference number | 16672372v1 |
| Volume Number | 103 |
| Issue Number | 20 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenocarcinoma of lung (disorder) Body tissue Carcinogenesis Deletion Mutation EGFR NP_005219.2:p.K29_N298insG EGFR protein, human Exons Glioblastoma Growth Factor Receptors HKI 272 In Vitro [Publication Type] Iressa Leukemia, B-Cell Lung Neoplasms Malignant Neoplasms Non-Small Cell Lung Carcinoma Protein Tyrosine Kinase Small cell carcinoma of lung Squamous cell carcinoma Squamous cell lung carcinoma Structure of parenchyma of lung erlotinib gefitinib |
| Content Type | Text |
| Resource Type | Article |
