ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
Tumor Analyses Reveal Squamous Transformation and Off-Target Alterations As Early Resistance Mechanisms to First-line Osimertinib in
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 257 papers, 6 of them syntheses that pooled it.
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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.
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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.
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Who cites it
257 citing papers in PubMed, 6 syntheses or guidelines pooled it, 374 citations in OpenAlex.
- Histological transformation in lung cancer: a single-arm meta-analysis and systematic review.BMC cancer · 2026Pooled it
- Efficacy and safety of antibody-drug conjugates in EGFR-mutant non-small cell lung cancer after tyrosine kinase inhibitor resistance: a systematic review and meta-analysis.Frontiers in oncology · 2026Pooled it
- What is the best first-line combination regimen for advanced EGFR-mutated non-small cell lung cancer: a network meta-analysis and systemic review.Frontiers in pharmacology · 2025Pooled it
- [Updated Interpretation of the NCCN Clinical Practice Guidelines (Version 3. 2023) for Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Guideline
- Exon-18-EGFR Mutated Transformed Small-Cell Lung Cancer: A Case Report and Literature Review.Current oncology (Toronto, Ont.) · 2023Pooled it
- Non-small cell lung cancer withFrontiers in oncology · 2023Pooled it
- Genomic Profiling of Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer after Progression on First-line Osimertinib: Phase II ORCHARD Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Phase 2 Study of Amivantamab Plus Lazertinib in Previously Treated Patients With EGFR-Mutant Lung Cancers With Brain and Leptomeningeal Metastases.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Trial
- A prospective, multicenter, comprehensive genomic profile signature study in patients with EGFR-mutant advanced non-small cell lung cancer at the first-line treatment failure of osimertinib.Signal transduction and targeted therapy · 2025Trial
- Lineage identity governs oncogene dependence in mouse NSCLC models of KRAS inhibitor resistance.Nature genetics · 2026Article
- Review
- Clinical utility of comprehensive genomic profiling in thoracic malignancies beyond conventional gene testing.International journal of clinical oncology · 2026Article
- Consistency of c-Met protein overexpression over time in patients with non-squamous non-small cell lung cancer.Histopathology · 2026Article
- EGFR-mutant NSCLC progressing on first-line osimertinib: rebiopsy in real-world and impact of second-line therapies (the "Rebiopsy on Osi" study).The oncologist · 2026Article
- Pragmatic Management of EGFR-Mutant NSCLC After Progression on Osimertinib: Canadian Expert Perspectives.Current oncology (Toronto, Ont.) · 2026Review
- Comparing Real-Time PCR and Amplicon-Based NGS for RoutineDiagnostics (Basel, Switzerland) · 2026Article
- Early-Phase Activation of Epithelial-Mesenchymal Transition in Lung Cancer Cells Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2026Article
- Inhibition of ferroptosis via SLC25A39-NRF2 axis drives Osimertinib resistance in lung adenocarcinoma.Cellular and molecular life sciences : CMLS · 2026Article
- KMT2D loss drives adeno-to-squamous transition and sensitizes TKI-resistant lung cancer to AURKA inhibition.Cell death and differentiation · 2026Article
- Coordinated DNA 5-mC and RNA mExperimental & molecular medicine · 2026Article
197 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
purposePatterns of resistance to first-line osimertinib are not well-established and have primarily been evaluated using plasma assays, which cannot detect histologic transformation and have differential sensitivity for copy number changes and chromosomal rearrangements. EXPERIMENTAL
designTo characterize mechanisms of resistance to osimertinib, patients with metastatic
resultsAmong 62 patients who met eligibility criteria, histologic transformation, primarily squamous transformation, was identified in 15% of first-line osimertinib cases and 14% of later-line cases. Nineteen percent (5/27) of patients treated with first-line osimertinib had off-target genetic resistance (2
conclusionsHistologic transformation and other off-target molecular alterations are frequent early emerging resistance mechanisms to osimertinib and are associated with poor clinical outcomes.
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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.