Trial reportCell reports. Medicine2020
Clonal Evolution and Heterogeneity of Osimertinib Acquired Resistance Mechanisms in EGFR Mutant Lung Cancer.
Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase II
In one paragraph
Trial report in Cell reports. Medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02759835 (A Pilot Study of Local Ablative Therapy for Treatment of Oligoprogressive, EGFR-mutated, Non-Small Cell Lung Cancer), which is not on this map. Cited by 132 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 2 pooled it
12.7field-weighted citation impact, top 1% of its field
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.
A Pilot Study of Local Ablative Therapy for Treatment of Oligoprogressive, EGFR-mutated, Non-Small Cell Lung Cancer (NSCLC) After Treatment With Osimertinib (AZD9291, Tagrisso)
Who cites it
132 citing papers in PubMed, 2 syntheses or guidelines pooled it, 174 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
- Non-small cell lung cancer withFrontiers in oncology · 2023Pooled it
- COMPEL: osimertinib plus platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC and progression on first-line osimertinib.ESMO open · 2025Trial
- Comprehensive genomic profiling of mucosal melanoma reveals novel fusion transcripts and dysregulation of cell-cycle, MAPK, and PI3K pathways.The Journal of pathology · 2026Article
- Longitudinal spatial multi-omics delineates tumor microenvironment remodeling across sequential EGFR-TKIs in EGFR-mutant NSCLC.Journal of translational medicine · 2026Article
- DRIVE: a comprehensive resource deciphering drug-induced transcriptomic and splicing response in cancer cell.Neoplasia (New York, N.Y.) · 2026Article
- Longitudinal In Vivo Imaging at Single-Lesion Resolution Identifies Allele-Associated Response and Resistance Dynamics in EGFR-Mutant Lung Cancer.International journal of molecular sciences · 2026Article
- Standardizing pCR/MPR Assessment in NSCLC After Neoadjuvant Therapy: Challenges and Perspectives.Cancers · 2026Review
- Molecular tumor board-guided osimertinib therapy in EGFR L858R/Q701L-mutant lung adenocarcinoma supported by functional validation.The oncologist · 2026Article
- Targeting ClassicalCancers · 2026Review
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Adaptive Regulation of dNTP Homeostasis Confers Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Carcinoma.Cancer research · 2026Article
- H4K8 lactylation-mediated ferroptosis defense drives EGFR-TKI resistance in lung adenocarcinoma.Apoptosis : an international journal on programmed cell death · 2026Article
- Non-enzymatic function of QSOX2 directly regulates the JUNB-ITGB4 axis and enhanced resistance to osimertinib in EGFR-mutation lung adenocarcinoma.Cell death discovery · 2026Article
- Longitudinal, Retrospective Use of a Circulating Tumor DNA Methylation Signature Successfully Captures Small Cell Evolution in a Patient With Metastatic EGFR-Mutant Non-Small Cell Lung Cancer.JCO precision oncology · 2026Article
- Mitotic Machinery Dysregulation in Lung Cancer: Biological Roles, Therapeutic Targeting, and Combination Strategies.Pharmaceutics · 2026Review
- Variant Allelic Frequency to Track Therapy Response and Evaluate Leptomeningeal Disease in Metastatic Central Nervous System Cancers.Diagnostics (Basel, Switzerland) · 2026Article
- Epigenetic priming promotes tyrosine kinase inhibitor resistance and oncogene amplification.Nature structural & molecular biology · 2026Article
- Efficacy and safety of first-line osimertinib monotherapy versus osimertinib plus platinum-based chemotherapy or amivantamab plus lazertinib in metastatic EGFR-mutated NSCLC: an indirect comparison.Frontiers in oncology · 2026Article
- Acquired BRAF-AGK Fusion Following Osimertinib Plus Savolitinib in EGFR-Mutated MET-Amplified Non-Small-Cell Lung Cancer: Durable Response to Gefitinib and Trametinib in a Case Report.OncoTargets and therapy · 2026Article
72 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
31 authors at 3 institutions in 1 country.
Nitin RoperThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Anna-Leigh BrownNational Center for Biotechnology Information, NIH, NLM, Bethesda, MD 20892, USA.
Jun S WeiThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Svetlana PackLaboratory of Pathology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Christopher TrindadeLaboratory of Pathology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Chul KimThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Olivia RestifoPresent address: Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC 20007, USA.
Shaojian GaoThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Sivasish SindiriGenetics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Farid MehrabadiCancer Data Science Laboratory, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Rajaa El MeskiniCenter for Advanced Preclinical Research, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Zoe Weaver OhlerCenter for Advanced Preclinical Research, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Tapan K MaityThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Abhilash VenugopalanThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Constance M CultraroThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Elizabeth AkothThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Emerson PadiernosThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Haobin ChenThoracic Surgery Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Aparna KesarwalaRadiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
DeeDee K SmartRadiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Naris NilubolSurgical Oncology Program, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Arun RajanThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Zofia PiotrowskaHematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Liqiang XiLaboratory of Pathology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Mark RaffeldLaboratory of Pathology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Anna R PanchenkoNational Center for Biotechnology Information, NIH, NLM, Bethesda, MD 20892, USA.
Cenk SahinalpCancer Data Science Laboratory, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Stephen HewittLaboratory of Pathology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Chuong D HoangThoracic Surgery Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Javed KhanGenetics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Udayan GuhaThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Center for Cancer Research · USNational Center for Biotechnology Information · USHarvard University · US
Funding
Experimental Pathology Laboratory (EPL)ZICBC011638 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HEWITT, STEPHEN · 2015 to 2025
$16.6MProtein phosphorylation downstream of mutant EGFR kinasesZIABC011410 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GUHA, UDAYAN · 2011 to 2020
$6.1MEpigenetic and immunologic aspects of neuroendocrine cancersZIABC011989 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ROPER, NITIN · 2020 to 2025
$5.8MDevelopment of FISH Molecular Diagnostics to support Clinical Trials at NCIZIDBC011792 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI XI, LIQIANG · 2017 to 2024
$4.5MDevelopment of Novel Preclinical Animal Models - CAPR InfrastructureZIGBC011735 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SHARAN, SHYAM · 2016 to 2025
$4.3MMetabolic imaging of the effects of brain radiotherapyZIABC011790 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SMART, DEEDEE · 2017 to 2025
$2.8MClinical Protocols in the Cancer Signaling Networks SectionZIABC011672 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GUHA, UDAYAN · 2016 to 2020
$2.7MIn-patient hospice and rapid autopsy to interrogate tumor heterogeneityZIABC011529 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GUHA, UDAYAN · 2013 to 2020
$2.1MDeveloping an Effective BET bromodomain inhibitor Drug Combo to Target SCLCZIABC011839 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CHEN, HAOBIN · 2018 to 2022
$1.8MAnti-PD-L1-TGFb antibody (M7824) in advanced Non-Small Cell Lung CancerZIABC011905 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RAJAN, ARUN · 2019 to 2025
$817kDurvalumab in Combination with Olaparib in Non-Small Cell Lung CancerZIABC011907 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RAJAN, ARUN · 2019 to 2025
$809kMolecular Mechanisms of Cancer DevelopmentZICBC011842 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PACK, SVETLANA · 2018 to 2020
$458kIntramural NIH HHS Z99 NH999999
Abstract
Clonal evolution of osimertinib-resistance mechanisms in EGFR mutant lung adenocarcinoma is poorly understood. Using multi-region whole-exome and RNA sequencing of prospectively collected pre- and post-osimertinib-resistant tumors, including at rapid autopsies, we identify a likely mechanism driving osimertinib resistance in all patients analyzed. The majority of patients acquire two or more resistance mechanisms either concurrently or in temporal sequence. Focal copy-number amplifications occur subclonally and are spatially and temporally separated from common resistance mutations such as
Indexed as
Carcinoma, Non-Small-Cell LungClonal EvolutionLung NeoplasmsAcrylamidesAdultAgedAged, 80 and overAniline CompoundsDrug Resistance, NeoplasmErbB ReceptorsExome SequencingFemaleGenetic HeterogeneityHumansIndolesMaleAcrylamidesAniline CompoundsEGFR protein, humanErbB ReceptorsIndolesosimertinibProtein Kinase InhibitorsPyrimidines
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390
Registered trials
NCT02759835ClinicalTrials.gov
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.