[HTML][HTML] KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib
PLoS medicine, 2005•journals.plos.org
Background 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. Methods and Findings We sought to determine whether
mutations in KRAS could be used to further enhance prediction of response to gefitinib or …
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. Methods and Findings We sought to determine whether
mutations in KRAS could be used to further enhance prediction of response to gefitinib or …
Background
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.
Methods and Findings
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.
Conclusion
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.
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