Emergence of EGFR G724S mutation in EGFR-mutant lung adenocarcinoma post progression on osimertinib
Abstract
Mutations in the epidermal growth factor receptor (EGFR) are drivers for a subset of lung cancers. Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) recently approved for the treatment of T790M-positive non-small cell lung cancer (NSCLC); however, acquired resistance to osimertinib is evident and resistance mechanisms remain incompletely defined. The EGFR G724S mutation was detected using hybrid-capture based comprehensive genomic profiling (CGP) and a hybrid-capture based circulating tumor DNA (ctDNA) assays in two cases of EGFR-driven lung adenocarcinoma in patients who had progressed on osimertinib treatment. This study demonstrates the importance of both tissue and blood based hybrid-capture based genomic profiling at disease progression to identifying novel resistance mechanisms in the clinic.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
G724S results in resistance to osimertinib in the presence of T790M.
“G724S also resides in the p-loop, and previous studies have shown that this mutation results in resistance to osimertinib in the presence of T790M[22].”
From Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib and Continuation Therapy Beyond Progression in <i>EGFR</i> -Mutant NSCLC (2018) · cites this paper as [22]
Cites
Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors
Sequist, L. V., Waltman, B. A., Dias-Santagata, D., Digumarthy, S., Turke, A. B., Fidias, P., Bergethon, K., Shaw, A. T., Gettinger, S., Cosper, A. K., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002003 · Cited by 3,499 · see citing works
Sequist, L. V., Yang, J. C.-H., Yamamoto, N., O'Byrne, K., Hirsh, V., Mok, T., Geater, S. L., Orlov, S., Tsai, C.-M., Boyer, M., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.44.2806 · Cited by 3,228 · see citing works
Frampton, G. M., Fichtenholtz, A., Otto, G. A., Wang, K., Downing, S. R., He, J., Schnall-Levin, M., White, J., Sanford, E. M., An, P., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2696 · Cited by 2,157 · see citing works
Lanman, R. B., Mortimer, S. A., Zill, O. A., Sebisanovic, D., Lopez, R., Blau, S., Collisson, E. A., Divers, S. G., Hoon, D. S. B., Kopetz, E. S., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0140712 · Cited by 695 · see citing works
Niederst, M. J., Hu, H., Mulvey, H. E., Lockerman, E. L., Garcia, A. R., Piotrowska, Z., Sequist, L. V., & Engelman, J. A. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0560 · Cited by 583 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Le, X., Puri, S., Negrao, M. V., Nilsson, M. B., Robichaux, J., Boyle, T., Hicks, J. K., Lovinger, K. L., Roarty, E., Rinsurongkawong, W., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1542 · Cited by 387 · see citing works
- Authors
- Oztan, A., Fischer, S., Schrock, A. B., Erlich, R. L., Lovly, C. M., Stephens, P. J., Ross, J. S., Miller, V., Ali, S. M., Ou, S.-H. I., & Raez, L. E.
- Affiliations
- Foundation Medicine (United States) (US)
- Vanderbilt University (US)
- University of California, Irvine (US)
- Memorial Healthcare System (US)
- Corresponding author
- Oztan, A.
- Venue
- Lung Cancer
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 111
- Pages
- 84-87
- ISSN
- 0169-5002 (ISSN-L)
- OpenAlex
- W2731518173
- Cited by
- 80
- References
- 5
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 9 · 2021: 15 · 2020: 13 · 2019: 12 · 2018: 15 · 2017: 2
- FWCI
- 9.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Lung Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- EGFR-mutant lung adenocarcinoma, osimertinib, acquired drug resistance, non-small cell lung cancer, circulating tumor DNA, resistance mechanisms, T790M
- MeSH terms
- Adenocarcinoma of Lung, Acrylamides, Adenocarcinoma, Aged, Alleles, Aniline Compounds, Antineoplastic Agents, Exons, Female, Humans, Indoles, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Piperazines, Pyrimidines, Tomography, X-Ray Computed, Treatment Outcome, Fatal Outcome, Disease Progression, Drug Resistance, Neoplasm, Amino Acid Substitution, Protein Kinase Inhibitors, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
