ArticleNature communications2025
Intratumor heterogeneity of EGFR expression mediates targeted therapy resistance and formation of drug tolerant microenvironment.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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.
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Who cites it
31 citing papers in PubMed.
- A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.Annals of medicine · 2026Review
- Longitudinal spatial multi-omics delineates tumor microenvironment remodeling across sequential EGFR-TKIs in EGFR-mutant NSCLC.Journal of translational medicine · 2026Article
- mRNA-based therapeutics in lung Cancer: Mechanisms, applications, and translational challenges.Journal, genetic engineering & biotechnology · 2026Review
- The logarithmic phase as a therapeutic direction: evaluating pharmacological strategies against cancer progression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Assessment of EGFR and HER2 expression in penile cancer as potential therapeutic targets.Virchows Archiv : an international journal of pathology · 2026Article
- 4-Anilinoquinazoline carbamate derivatization as a platform for prodrug design and localized drug delivery.Bioorganic chemistry · 2026Article
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- Mesenchymal stem cell-induced metabolic reprogramming of EGFR-wild-type tumor cells drives therapeutic resistance in EGFR-mutant non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- High-fidelity super-resolution CT radiomics for non-invasive EGFR mutation prediction in lung adenocarcinoma: a multi-center pooled analysis.La Radiologia medica · 2026Article
- Reciprocal signaling-metabolic crosstalk between fibroblasts and tumor cells drives cetuximab tolerance in head and neck cancers.Journal of experimental & clinical cancer research : CR · 2026Article
- Universal diseased-site targeting via glycolysis-driven lactic acid gradient.Science advances · 2026Article
- Tumor microenvironment-specific nanomedicine: from biology-driven to multi-omics-guided precision engineering.Journal of hematology & oncology · 2026Review
- Wogonin-Loaded PLGA Sustained-Release Nanomicelle Inhibiting EGFR Pathway for Antitumor Effects in OSCC.ACS omega · 2026Article
- AnnQ: reference-based quantification of cellular abnormality at single-cell resolution.Briefings in bioinformatics · 2026Article
- Optimizing next-generation CAR-macrophages against solid tumors: challenges and potential strategies.Journal of hematology & oncology · 2026Review
- Chemotherapy Supports Cancer Cell Dissemination in a Melanoma Preclinical Model.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies.JTO clinical and research reports · 2026Review
- Global trends and research progress on immunotherapy forJournal of thoracic disease · 2026Article
- Frontiers in Cell-Cycle-Targeting Therapies: Addressing the Heterogeneity of the Cancer Cell Cycle.Cancers · 2026Article
- Combined Assessment of EZH2 and EGFR as Potential Diagnostic Biomarkers for Epithelial Ovarian Tumors: Bioinformatics Analysis and Clinical Validation.International journal of women's health · 2026Article
Corrections and comments
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Authors and funding
28 authors.
Funding
Abstract
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used to treat non-small cell lung cancers with EGFR mutations, but drug resistance often emerges. Intratumor heterogeneity is a known cause of targeted therapy resistance and is considered a major factor in treatment failure. This study identifies clones of EGFR-mutant non-small cell lung tumors expressing low levels of both wild-type and mutant EGFR protein. These EGFR-low cells are intrinsically more tolerant to EGFR inhibitors, more invasive, and exhibit an epithelial-to-mesenchymal-like phenotype compared to their EGFR-high counterparts. The EGFR-low cells secrete Transforming growth factor beta (TGFβ) family cytokines, leading to increased recruitment of cancer-associated fibroblasts and immune suppression, thus contributing to the drug-tolerant tumor microenvironment. Notably, pharmacological induction of EGFR using epigenetic inhibitors sensitizes the resistant cells to EGFR inhibition. These findings suggest that intrinsic drug resistance can be prevented or reversed using combination therapies.
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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.