Loading...
Please wait, while we are loading the content...
Similar Documents
Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Taron, Miguel Ichinose, Yukito Rosell, Rafael Mok, Tony Shu Kam Massutí, Bartomeu Zamora, Lurdes Maté, José Luis Manegold, Christian Ono, Mayumi Queralt, Cristina Sánchez, José Javier Sánchez-Ronco, María Hsue, Victor Jablons, David Mark Sánchez, Jose Miguel Couselo Morán, Teresa |
| Copyright Year | 2005 |
| Abstract | PURPOSE Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) confer a strong sensitivity to gefitinib, a selective tyrosine kinase inhibitor of EGFR. EXPERIMENTAL DESIGN We examined EGFR mutations at exons 18, 19, and 21 in tumor tissue from 68 gefitinib-treated, chemorefractory, advanced non-small cell lung cancer patients from the United States, Europe, and Asia and in a highly gefitinib-sensitive non-small cell lung cancer cell line and correlated their presence with response and survival. In addition, in a subgroup of 28 patients for whom the remaining tumor tissue was available, we examined the relationship among EGFR mutations, CA repeats in intron 1 of EGFR, EGFR and caveolin-1 mRNA levels, and increased EGFR gene copy numbers. RESULTS Seventeen patients had EGFR mutations, all of which were in lung adenocarcinomas. Radiographic response was observed in 16 of 17 (94.1%) patients harboring EGFR mutations, in contrast with 6 of 51 (12.6%) with wild-type EGFR (P < 0.0001). Probability of response increased significantly in never smokers, patients receiving a greater number of prior chemotherapy regimens, Asians, and younger patients. Median survival was not reached for patients with EGFR mutations and was 9.9 months for those with wild-type EGFR (P = 0.001). EGFR mutations tended to be associated with increased numbers of CA repeats and increased EGFR gene copy numbers but not with EGFR and caveolin-1 mRNA overexpression (P = not significant). CONCLUSIONS The presence of EGFR mutations is a major determinant of gefitinib response, and targeting EGFR should be considered in preference to chemotherapy as first-line treatment in lung adenocarcinomas that have demonstrable EGFR mutations. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://clincancerres.aacrjournals.org/content/clincanres/11/16/5878.full.pdf |
| PubMed reference number | 16115929v1 |
| Volume Number | 11 |
| Issue Number | 16 |
| Journal | Clinical cancer research : an official journal of the American Association for Cancer Research |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenocarcinoma Chemotherapy-Induced Febrile Neutropenia EGFR protein, human Exons Growth Factor Receptors Introns Lung diseases Mutation Neoplasms Non-Small Cell Lung Carcinoma Patients Protein Tyrosine Kinase Protein-tyrosine kinase inhibitor Small cell carcinoma of lung Structure of parenchyma of lung Tyrosine Kinase Domain cancer cell cellular targeting gefitinib tumor tissue |
| Content Type | Text |
| Resource Type | Article |
