{"entity":{"id":"paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013","kind":"paper","name":"Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers","aka":[],"tldr":"Rebiopsying 155 patients whose targeted pill had stopped working put numbers on how they escape: about two thirds by one mutation, a few by making extra copies of another receptor, and a few by turning into a different kind of cancer altogether.","summary":"Patients with lung adenocarcinoma and acquired resistance to erlotinib or gefitinib enrolled in a prospective biopsy protocol and underwent rebiopsy after resistance developed. Histology was reviewed and samples genotyped for mutations in EGFR, AKT1, BRAF, ERBB2, KRAS, MEK1, NRAS and PIK3CA, with fluorescence in situ hybridisation for MET and HER2. Adequate samples were obtained in 155 patients. Ninety-eight had a second-site EGFR T790M mutation, 63%, and four had small-cell transformation, 3%. MET amplification was seen in 4 of 75, 5%, and HER2 amplification in 3 of 24, 13%. No acquired mutations were detected in PIK3CA, AKT1, BRAF, ERBB2, KRAS, MEK1 or NRAS among 88 tested. Overlap between mechanisms was seen in 4%.","asOf":"2026-09-25","links":[{"label":"Yu et al., Clin Cancer Res 2013: rebiopsy at acquired resistance in 155 patients with EGFR-mutant lung cancer","url":"https://doi.org/10.1158/1078-0432.CCR-12-2246"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23470965/"}],"tags":[],"related":["egfr-t790m","met-amplification-readout"],"cancers":["nsclc","sclc"],"sections":[],"technologies":["cytogenetics-fish","cgp"],"targets":["egfr","met","her2"],"drugs":["erlotinib","gefitinib"],"companies":[],"institutions":["mskcc"],"pathways":["resistance-routes-map","rtk-activation","lineage-plasticity-neuroendocrine"],"terms":["resistance","histologic-transformation","met-amplification","biopsy"],"trials":[],"people":["gregory-riely"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2013,"doi":"10.1158/1078-0432.CCR-12-2246","pmid":"23470965","authors":"Yu HA, Arcila ME, Rekhtman N, et al.","paperType":"observational","findings":["T790M in 98 of 155 rebiopsied patients, 63%, the dominant mechanism.","MET amplification in 5% and HER2 amplification in 13% of those tested for them.","Small-cell transformation in 3%.","No acquired mutations in the downstream pathway genes tested."],"whatItMeans":"It is the reference frequency table for resistance to first-generation EGFR inhibitors, and it made rebiopsy at progression standard rather than exceptional, because the mechanism decides the next treatment and cannot be guessed.","caveats":["Only patients whose disease could be safely rebiopsied were included, which selects for accessible lesions.","A limited gene set was tested, so mechanisms outside it were not counted.","Single centre."],"changedPractice":true,"participants":155},"route":"/key-papers/paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013/","neighbours":{"biomarker":[{"id":"egfr-t790m","kind":"biomarker","name":"EGFR T790M","route":"/biomarkers/egfr-t790m/"},{"id":"met-amplification-readout","kind":"biomarker","name":"MET amplification (gene copy number)","route":"/biomarkers/met-amplification-readout/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"drug":[{"id":"erlotinib","kind":"drug","name":"Erlotinib","route":"/drugs/erlotinib/"},{"id":"gefitinib","kind":"drug","name":"Gefitinib","route":"/drugs/gefitinib/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"}],"term":[{"id":"biopsy","kind":"term","name":"Biopsy","route":"/terms/biopsy/"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"histologic-transformation","kind":"term","name":"Histologic transformation","route":"/terms/histologic-transformation/"},{"id":"met-amplification","kind":"term","name":"MET amplification (bypass resistance)","route":"/terms/met-amplification/"}],"person":[{"id":"gregory-riely","kind":"person","name":"Gregory J. Riely","route":"/people/gregory-riely/"}],"journal":[{"id":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","route":"/journals/clinical-cancer-research/"}]}}