{"entity":{"id":"paper-paez-egfr-mutations-gefitinib-science-2004","kind":"paper","name":"EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy","aka":[],"tldr":"The second of the two 2004 papers that found EGFR mutations. It also explained why Japanese patients responded to gefitinib far more often than American ones: the mutation was simply much more common in Japan.","summary":"Paez, Jänne, Lee and colleagues at the Dana-Farber Cancer Institute and the Broad Institute, with Meyerson as senior author, sequenced receptor tyrosine kinase genes in non-small-cell lung cancer and matched normal tissue, then looked for the same mutations in responders to gefitinib and in a hypersensitive cell line.\n\nThe geographic difference it documented is the paper's second contribution. A response rate that varied by country had been read as a difference in practice or reporting; it turned out to be a difference in the prevalence of a mutation, which is the first demonstration in lung cancer that tumour genotype, not population, explains a drug's performance.","asOf":"2026-09-25","links":[{"label":"Science 2004","url":"https://doi.org/10.1126/science.1099314"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15118125/"}],"tags":["lung-evidence"],"related":["paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009","targeted-therapy-roadmap"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc","lung-adenocarcinoma"],"sections":["targeted-therapy","diagnostics"],"technologies":["ngs"],"targets":["egfr"],"drugs":["gefitinib"],"companies":[],"institutions":["dana-farber","broad-institute"],"pathways":["ras-mapk"],"terms":["driver-mutation","oncogene-addiction"],"trials":[],"people":["pasi-janne","matthew-meyerson"],"bottlenecks":["b-biomarker-validation","b-trial-diversity"],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2004,"doi":"10.1126/science.1099314","pmid":"15118125","authors":"Paez JG, Jänne PA, Lee JC, et al.","paperType":"translational","findings":["Somatic EGFR mutations were found in 15 of 58 unselected tumours from Japan and in 1 of 61 from the United States.","EGFR mutations were found in additional samples from United States patients who responded to gefitinib, and in a lung adenocarcinoma cell line hypersensitive to gefitinib.","No EGFR mutations were found in gefitinib-insensitive tumours or cell lines."],"whatItMeans":"Why a drug can look useless in one trial and transformative in another: the trials had different proportions of the patients the drug was for. It is the argument for genotyping before drawing conclusions from a response rate.","caveats":["Small, unbalanced cohorts (58 Japanese and 61 United States tumours) and a retrospective response comparison.","Sequencing of selected receptor tyrosine kinase genes, not the genome; other drivers in the same tumours were not looked for.","Prevalence estimates from tumour series of that era are not population estimates."],"changedPractice":true},"route":"/key-papers/paper-paez-egfr-mutations-gefitinib-science-2004/","neighbours":{"paper":[{"id":"paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","kind":"paper","name":"Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib","route":"/key-papers/paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004/"},{"id":"paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009","kind":"paper","name":"Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma","route":"/key-papers/paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009/"}],"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}],"cancer":[{"id":"lung-adenocarcinoma","kind":"cancer","name":"Adenocarcinoma of the lung","route":"/cancers/lung-adenocarcinoma/"},{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"term":[{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"oncogene-addiction","kind":"term","name":"Oncogene addiction","route":"/terms/oncogene-addiction/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}],"drug":[{"id":"gefitinib","kind":"drug","name":"Gefitinib","route":"/drugs/gefitinib/"}],"institution":[{"id":"broad-institute","kind":"institution","name":"Broad Institute of MIT and Harvard","route":"/institutions/broad-institute/"},{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"person":[{"id":"matthew-meyerson","kind":"person","name":"Matthew Meyerson","route":"/people/matthew-meyerson/"},{"id":"pasi-janne","kind":"person","name":"Pasi A. Jänne","route":"/people/pasi-janne/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-trial-diversity","kind":"bottleneck","name":"Trials do not represent the people who get cancer","route":"/bottlenecks/b-trial-diversity/"}],"journal":[{"id":"science","kind":"journal","name":"Science","route":"/journals/science/"}]}}