ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2024
MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 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
33 citing papers in PubMed, 38 citations in OpenAlex.
- ABL209 (NEOK002): Designing an EGFR × MUC1 Bispecific TOP1i ADC with Promising Antitumor Activity and Enhanced Therapeutic Window.Molecular cancer therapeutics · 2026Article
- Flavokawain A inhibits high glucose-induced malignant progression of lung cancer cells by suppressing PRMT5-mediated PTEN neddylation and nuclear translocation.Oncology letters · 2026Article
- M1C is a druggable target for NSCLC KRAS G12C mutant tumors resistant to KRAS inhibitors.Oncogene · 2026Article
- Prognostic and therapeutic importance of TROP-2 and MUC-1 in non-small cell lung cancer: A systematic review and meta-analysis.Biomedical reports · 2026Article
- The neural stem cell‑NSCLC axis: Molecular drivers, microenvironment crosstalk and emerging therapies (Review).International journal of oncology · 2026Review
- USP20-mediated PGAM1 stabilization promotes glycolysis and confers osimertinib resistance in non-small cell lung carcinoma.Oncogene · 2026Article
- M1C IS NECESSARY FOR DARAXONRASIB RESISTANCE OF NSCLC KRAS(G12C) MUTANT CELLS.bioRxiv : the preprint server for biology · 2026Article
- Evolution of the MUC1 gene in eutherian mammals as an adaptation responsible for the increasing incidence of cancer in humans.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- MUC1 promotes NSCLC progression by regulating ICAM-1-mediated mitochondria transfer from tCAFs to cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Postoperative pain score and infection risk in lung cancer resection: a propensity score-matching study.American journal of translational research · 2026Article
- Clinical applications of antibody-drug conjugates in advanced non-small cell lung cancer.Frontiers in immunology · 2026Review
- Sorafenib Resistance in Hepatocellular Carcinoma: Emerging Molecular Insights from Long Non-Coding RNAs.Current pharmaceutical design · 2026Review
- Targeting KRAS Inhibitor-Resistant Pancreatic Cancer with an MUC1-C Antibody-Drug Conjugate.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- MUCIN 1 confers inflammatory memory of tyrosine kinase inhibitor resistance in non-small cell lung cancer.Signal transduction and targeted therapy · 2025Article
- Eradicating Drug-tolerant Persister Cells in EGFR-Mutated Non-Small Cell Lung Cancer by Targeting TROP2 with CAR-T Cellular Therapy.Cancer discovery · 2025Article
- EGFR Targeted Liposomal PROTAC Assisted With Epigenetic Regulation as an Efficient Strategy for Osimertinib-Resistant Lung Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- MUC1-C auto-regulatory complex with EBNA1 is responsible for latent Epstein-Barr virus-associated gastric cancer progression.Oncogene · 2025Article
- Activation of APOBEC3 cytidine deaminases and endogenous retroviruses is integrated by MUC1-C in NSCLC cells.Cell death discovery · 2025Article
- The next generation of immunotherapies for lung cancers.Nature reviews. Clinical oncology · 2025Review
- Single-cell and spatial transcriptomics profile the interaction ofTranslational lung cancer research · 2025Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
introductionOsimertinib is an irreversible EGFR tyrosine kinase inhibitor approved for the first-line treatment of patients with metastatic NSCLC harboring EGFR exon 19 deletions or L858R mutations. Patients treated with osimertinib invariably develop acquired resistance by mechanisms involving additional EGFR mutations, MET amplification, and other pathways. There is no known involvement of the oncogenic MUC1-C protein in acquired osimertinib resistance.
methodsH1975/EGFR (L858R/T790M) and patient-derived NSCLC cells with acquired osimertinib resistance were investigated for MUC1-C dependence in studies of EGFR pathway activation, clonogenicity, and self-renewal capacity.
resultsWe reveal that MUC1-C is up-regulated in H1975 osimertinib drug-tolerant persister cells and is necessary for activation of the EGFR pathway. H1975 cells selected for stable osimertinib resistance (H1975-OR) and MGH700-2D cells isolated from a patient with acquired osimertinib resistance are found to be dependent on MUC1-C for induction of (1) phospho (p)-EGFR, p-ERK, and p-AKT, (2) EMT, and (3) the resistant phenotype. We report that MUC1-C is also required for p-EGFR, p-ERK, and p-AKT activation and self-renewal capacity in acquired osimertinib-resistant (1) MET-amplified MGH170-1D #2 cells and (2) MGH121 Res#2/EGFR (T790M/C797S) cells. Importantly, targeting MUC1-C in these diverse models reverses osimertinib resistance. In support of these results, high MUC1 mRNA and MUC1-C protein expression is associated with a poor prognosis for patients with EGFR-mutant NSCLCs.
conclusionsOur findings reveal that MUC1-C is a common effector of osimertinib resistance and is a potential target for the treatment of osimertinib-resistant NSCLCs.
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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 Socratic graph.