KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib
Top Cited Papers
Open Access
- 25 January 2005
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Medicine
- Vol. 2 (1) , e17
- https://doi.org/10.1371/journal.pmed.0020017
Abstract
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.Keywords
This publication has 13 references indexed in Scilit:
- Mutations and addiction to EGFR: the Achilles ‘heal’ of lung cancers?Trends in Molecular Medicine, 2004
- Intragenic ERBB2 kinase mutations in tumoursNature, 2004
- EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinibProceedings of the National Academy of Sciences, 2004
- Gefitinib-Sensitizing EGFR Mutations in Lung Cancer Activate Anti-Apoptotic PathwaysScience, 2004
- EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib TherapyScience, 2004
- Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to GefitinibNew England Journal of Medicine, 2004
- New Guidelines to Evaluate the Response to Treatment in Solid TumorsJNCI Journal of the National Cancer Institute, 2000
- TherasOncogenes in Human Lung CancerAmerican Review of Respiratory Disease, 1990
- DETECTION OF RAS GENE-MUTATIONS IN HUMAN LUNG CANCERS BY SINGLE-STRAND CONFORMATION POLYMORPHISM ANALYSIS OF POLYMERASE CHAIN-REACTION PRODUCTS1990
- INCIDENCE AND POSSIBLE CLINICAL-SIGNIFICANCE OF K-RAS ONCOGENE ACTIVATION IN ADENOCARCINOMA OF THE HUMAN-LUNG1988