ArticleCancer research2015
Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
174 citing papers in PubMed, 1 synthesis or guideline pooled it, 294 citations in OpenAlex.
- Efficacy and safety of osimertinib in treating EGFR-mutated advanced NSCLC: A meta-analysis.International journal of cancer · 2019Pooled it
- Neoadjuvant Aumolertinib for unresectable stage III EGFR-mutant non-small cell lung cancer: a single-arm phase II trial.Nature communications · 2025Trial
- Review
- TGM2-TUFM promotes acquired resistance to EGFR-TKIs in EGFR-mutated NSCLC through p62-mediated lipophagy.Respiratory research · 2026Article
- Altered Sphingolipid Metabolism is Associated with Osimertinib Resistance in Nonsmall-Cell Lung Cancer.Journal of proteome research · 2026Article
- Stanniocalcin 2-Induced Autophagy Confers Resistance of Lung Cancer Cells to EGFR Inhibition via the ERK/Beclin 1 Signaling.Cancer medicine · 2026Article
- Precision Medicine in Treating Lung Cancer: A Narrative Review on Treatments Targeting Oncogenic Genetic Mutations.Cureus · 2026Review
- Review
- Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation.Cell communication and signaling : CCS · 2026Article
- Bevacizumab Plus EGFR-TKIs vs EGFR-TKIs Alone for Advanced EGFR-Mutant NSCLC: A Meta-Analysis.Clinical Medicine Insights. Oncology · 2026Article
- The evolving landscape of first-line and subsequent therapies inExploration of targeted anti-tumor therapy · 2026Review
- SOS1 inhibition suppresses the emergence of osimertinib resistance to generate a durable response inScience signaling · 2025Article
- Understanding and overcoming multidrug resistance in cancer.Nature reviews. Clinical oncology · 2025Review
- Strategies Beyond 3rd EGFR-TKI Acquired Resistance: Opportunities and Challenges.Cancer medicine · 2025Review
- Integrated machine learning to predict the prognosis of lung adenocarcinoma patients based on SARS-COV-2 and lung adenocarcinoma crosstalk genes.Cancer science · 2025Article
- Furopyridine Derivatives as Potent Inhibitors of the Wild Type, L858R/T790M, and L858R/T790M/C797S EGFR.The journal of physical chemistry. B · 2024Article
- Aberrant expression of MRAS and HEG1 as the biomarkers for osimertinib resistance in LUAD.Discover oncology · 2024Article
- Triple-targeted therapy of dabrafenib, trametinib, and osimertinib for the treatment of the acquiredTranslational lung cancer research · 2024Article
- Overcoming Secondary Mutations of Type II Kinase Inhibitors.Journal of medicinal chemistry · 2024Review
- SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.Molecular oncology · 2024Article
114 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 1 institution in 1 country.
Funding
Abstract
Resistance to targeted EGFR inhibitors is likely to develop in EGFR-mutant lung cancers. Early identification of innate or acquired resistance mechanisms to these agents is essential to direct development of future therapies. We describe the detection of heterogeneous mechanisms of resistance within populations of EGFR-mutant cells (PC9 and/or NCI-H1975) with acquired resistance to current and newly developed EGFR tyrosine kinase inhibitors, including AZD9291. We report the detection of NRAS mutations, including a novel E63K mutation, and a gain of copy number of WT NRAS or WT KRAS in cell populations resistant to gefitinib, afatinib, WZ4002, or AZD9291. Compared with parental cells, a number of resistant cell populations were more sensitive to inhibition by the MEK inhibitor selumetinib (AZD6244; ARRY-142886) when treated in combination with the originating EGFR inhibitor. In vitro, a combination of AZD9291 with selumetinib prevented emergence of resistance in PC9 cells and delayed resistance in NCI-H1975 cells. In vivo, concomitant dosing of AZD9291 with selumetinib caused regression of AZD9291-resistant tumors in an EGFRm/T790M transgenic model. Our data support the use of a combination of AZD9291 with a MEK inhibitor to delay or prevent resistance to AZD9291 in EGFRm and/or EGFRm/T790M tumors. Furthermore, these findings suggest that NRAS modifications in tumor samples from patients who have progressed on current or EGFR inhibitors in development may support subsequent treatment with a combination of EGFR and MEK inhibition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.