{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["9(1)"],"submitter":["Wang Y"],"funding":["Blueprint Medicines"],"pubmed_abstract":["Fourth-generation EGFR tyrosine kinase are in development to overcome common resistance mutations. We performed deep mutational scanning (DMS) of the EGFR kinase domain in the context of L858R by introducing a saturation library of ~17,000 variants into Ba/F3 cells. DMS library-expressing cells were exposed to osimertinib or BLU-945 to identify escape mutations. L718X mutations were enriched across all conditions. BLU-945 specific mutations included K714R, K716T, L718V, T725M, K728E, K754E/N, N771S/T, T783I, Q791L/K, G863S, S895N, K929I, and M971L. A secondary DMS screen combining osimertinib and BLU-945, exclusively enriched for L718X mutations. Clinically, L718X mutations emerged in two patients treated with BLU-945. One patient with baseline EGFR L858R and L718Q mutations experienced ea"],"journal":["NPJ precision oncology"],"pagination":["294"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12368022"],"repository":["biostudies-literature"],"pubmed_title":["Deep mutational scanning reveals EGFR mutations conferring resistance to the 4th-generation EGFR tyrosine kinase inhibitor BLU-945."],"pmcid":["PMC12368022"],"pubmed_authors":["Papoian G","Shum E","Ranieri M","Moore XTR","Deng J","Wong KK","Hao Y","Hollenberg M","Sherman F","Poirier JT","Tsidilkovski L","Abramyan TM","Saribekyan H","Wang Y","Lopez A"],"additional_accession":[]},"is_claimable":false,"name":"Deep mutational scanning reveals EGFR mutations conferring resistance to the 4th-generation EGFR tyrosine kinase inhibitor BLU-945.","description":"Fourth-generation EGFR tyrosine kinase are in development to overcome common resistance mutations. We performed deep mutational scanning (DMS) of the EGFR kinase domain in the context of L858R by introducing a saturation library of ~17,000 variants into Ba/F3 cells. DMS library-expressing cells were exposed to osimertinib or BLU-945 to identify escape mutations. L718X mutations were enriched across all conditions. BLU-945 specific mutations included K714R, K716T, L718V, T725M, K728E, K754E/N, N771S/T, T783I, Q791L/K, G863S, S895N, K929I, and M971L. A secondary DMS screen combining osimertinib and BLU-945, exclusively enriched for L718X mutations. Clinically, L718X mutations emerged in two patients treated with BLU-945. One patient with baseline EGFR L858R and L718Q mutations experienced ea","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-06-03T06:36:19.813Z","creation":"2026-04-25T03:20:47.993Z"},"accession":"S-EPMC12368022","cross_references":{"pubmed":["40836025"],"doi":["10.1038/s41698-025-01086-2"]}}