ArticleNature communications2021
Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Resistance Mutation Profiles Associated with Current Treatments for Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer in the United States: A Systematic Literature Review.Current oncology (Toronto, Ont.) · 2025Pooled it
- A Phase II trial of alternating osimertinib and gefitinib therapy in advanced EGFR-T790M positive non-small cell lung cancer: OSCILLATE.Nature communications · 2024Trial
- PIK3CA in the transformation of EGFR ‑mutant lung adenocarcinoma to small cell lung cancer following acquired targeted therapy resistance.Chinese medical journal · 2026Article
- AKT Inhibitor Capivasertib as a Target for Osimertinib Combination Therapy in Lung Adenocarcinoma withGenes · 2026Article
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- Dynamic ecosystems of tumor drug resistance mechanisms: from molecular heterogeneity to systemic interventions.Apoptosis : an international journal on programmed cell death · 2026Review
- Nanotechnology-Assisted Molecular Profiling: Emerging Advances in Circulating Tumor DNA Detection.International journal of nanomedicine · 2026Review
- Nanopore based RNA methylation profiling of a circulating lung cancer biomarker.Communications medicine · 2025Article
- Clinical benefit of additional whole-exome sequencing over panel sequencing in an all-comer real-world molecular tumor board.ESMO open · 2025Article
- Real-world treatment outcomes in South Korean patients with epidermal growth factor receptor-mutant non-small cell lung cancer.The Korean journal of internal medicine · 2025Article
- A narrative review of imaging intratumor heterogeneity in non-small cell lung cancer: current advances.Translational lung cancer research · 2025Review
- Circulating tumor DNA in lung cancer: a bibliometric analysis of studies published from 2001 to 2024.Journal of thoracic disease · 2025Article
- CircSPINT2 confers sensitivity to osimertinib via hsa-miR-1296-3p/RBP1 axis and inhibits NSCLC progression.Molecular therapy. Oncology · 2025Article
- Extracellular Vesicles for Clinical Diagnostics: From Bulk Measurements to Single-Vesicle Analysis.ACS nano · 2025Review
- Review
- Osimertinib for EGFR-Mutant NSCLC Patients With Acquired T790M and EGFR Amplification After First-Generation EGFR-TKI Resistance.Cancer science · 2025Article
- Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis.Neoplasia (New York, N.Y.) · 2025Article
- Evaluation of EGFR-TKIs and ICIs treatment stratification in non-small cell lung cancer using an encrypted multidimensional radiomics approach.Cancer imaging : the official publication of the International Cancer Imaging Society · 2025Article
- Comparison of tissue-based and plasma-based testing for EGFR mutation in non-small cell lung cancer patients.Journal of pathology and translational medicine · 2025Article
- Base editing screens define the genetic landscape of cancer drug resistance mechanisms.Nature genetics · 2024Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
Abstract
Advanced non-small-cell lung cancer (NSCLC) patients with EGFR T790M-positive tumours benefit from osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Here we show that the size of the EGFR T790M-positive clone impacts response to osimertinib. T790M subclonality, as assessed by a retrospective NGS analysis of 289 baseline plasma ctDNA samples from T790M-positive advanced NSCLC patients from the AURA3 phase III trial, is associated with shorter progression-free survival (PFS), both in the osimertinib and the chemotherapy-treated patients. Both baseline and longitudinal ctDNA profiling indicate that the T790M subclonal tumours are enriched for PIK3CA alterations, which we demonstrate to confer resistance to osimertinib in vitro that can be partially reversed by PI3K pathway inhibitors. Overall, our results elucidate the impact of tumour heterogeneity on response to osimertinib in advanced stage NSCLC patients and could help define appropriate combination therapies in these patients.
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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.