KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib

Somatic mutations in the gene for the epidermal growth factor receptor (EGFR) are found in adenocarcinomas of the lung and are associated with sensitivity to the kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Lung adenocarcinomas also harbor activating mutations in the downstream GTPa...

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Bibliographic Details
Published in:PLoS medicine 2005-01, Vol.2 (1), p.e17-e17
Main Authors: Pao, William, Wang, Theresa Y, Riely, Gregory J, Miller, Vincent A, Pan, Qiulu, Ladanyi, Marc, Zakowski, Maureen F, Heelan, Robert T, Kris, Mark G, Varmus, Harold E
Format: Article
Language:English
Subjects:
Adenocarcinoma - drug therapy
Adenocarcinoma - genetics
Antineoplastic Agents - pharmacology
Cancer: Lung
Capillary electrophoresis
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
Clinical trials
Decision Making
Drug Resistance, Neoplasm
Epidermal growth factor
Erlotinib Hydrochloride
Genes, ras
Genetics
Genetics/Genomics/Gene Therapy
Humans
Kinases
Lung cancer
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Medical research
Mutation
Oncology
Patients
Quinazolines - pharmacology
Research funding
Treatment Outcome
Tumors
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Summary:Somatic mutations in the gene for the epidermal growth factor receptor (EGFR) are found in adenocarcinomas of the lung and are associated with sensitivity to the kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Lung adenocarcinomas also harbor activating mutations in the downstream GTPase, KRAS, and mutations in EGFR and KRAS appear to be mutually exclusive. We sought to determine whether mutations in KRAS could be used to further enhance prediction of response to gefitinib or erlotinib. We screened 60 lung adenocarcinomas defined as sensitive or refractory to gefitinib or erlotinib for mutations in EGFR and KRAS. We show that mutations in KRAS are associated with a lack of sensitivity to either drug. Our results suggest that treatment decisions regarding use of these kinase inhibitors might be improved by determining the mutational status of both EGFR and KRAS.
ISSN:1549-1676
1549-1277
1549-1676
DOI:10.1371/journal.pmed.0020017