{"entity":{"id":"c797s","kind":"term","name":"EGFR C797S","aka":[],"tldr":"A mutation that stops osimertinib from binding to EGFR; the main on-target way lung cancers escape it.","summary":"EGFR C797S is a mutation at the covalent binding site that stops osimertinib from attaching to EGFR, and it is the main on-target route by which lung cancers escape the drug. It arises in a minority of patients progressing on osimertinib, either in cis or in trans with T790M, and it can be detected in circulating tumour DNA by liquid biopsy. No fourth-generation EGFR inhibitor is yet approved, with BLU-945 and others discontinued or still early, so amivantamab-based and antibody-drug conjugate regimens are the practical answer. The first-line pairing of amivantamab and lazertinib is designed partly to pre-empt this escape route. The term belongs to the wider topic of acquired resistance and appears in the resistance-routes map and the drug-tolerant persister pathway.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Osimertinib","links":[{"label":"Thress et al., Acquired EGFR C797S mutation mediates resistance to AZD9291 (Nature Medicine 2015)","url":"https://doi.org/10.1038/nm.3854"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy"],"targets":["egfr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-thress-nat-med"],"journals":[],"dependsOn":[],"notes":[],"category":"Resistance"},"route":"/terms/c797s/","neighbours":{"cancer":[{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}],"term":[{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"}],"paper":[{"id":"paper-thress-nat-med","kind":"paper","name":"Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M","route":"/key-papers/paper-thress-nat-med/"}],"pairing":[{"id":"amivantamab-plus-lazertinib","kind":"pairing","name":"Amivantamab + lazertinib (first-line EGFR NSCLC)","route":"/pairings/amivantamab-plus-lazertinib/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"}],"pathway":[{"id":"drug-tolerant-persisters","kind":"pathway","name":"Drug-tolerant persister cells","route":"/pathways/drug-tolerant-persisters/"},{"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/"}],"biomarker":[{"id":"egfr-t790m","kind":"biomarker","name":"EGFR T790M","route":"/biomarkers/egfr-t790m/"}]}}