ArticleCancer discovery2025
Eradicating Drug-tolerant Persister Cells in EGFR-Mutated Non-Small Cell Lung Cancer by Targeting TROP2 with CAR-T Cellular Therapy.
Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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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
23 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Treatment prioritization of chemotherapy-anchored regimens after EGFR-TKI failure in EGFR-mutant NSCLC: a systematic review, pairwise meta-analysis and Bayesian network meta-analysis with probabilistic multi-criteria decision analysis.Frontiers in immunology · 2026Pooled it
- ctDNA clearance predicts survival in unresectable EGFR-mutant NSCLC: a meta-analysis.Frontiers in oncology · 2026Pooled it
- Tumor-infiltrating plasma cell profiling after PD-1 blockade reveals tumor-specific antibodies.Cancer cell · 2026Article
- Review
- Lung tumour secretome and extracellular vesicles: mechanisms, biomarkers, and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Trophoblast cell-surface antigen 2-targeted "sacituzumab tirumotecan": a new approach for epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small cell lung cancer.Translational lung cancer research · 2026Article
- Anti-TROP2 Antibody Drug Conjugates in EGFR-Mutant Non-Small Cell Lung Cancer: Biological Rationale and Clinical Challenges.Pharmaceutics · 2026Review
- Review
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Evaluating datopotamab deruxtecan (Dato-DXd) as a novel treatment option for EGFR-mutated non-small cell lung cancer.Future oncology (London, England) · 2026Review
- TROP2 expression as a prognostic predictor for osimertinib in patients withTranslational lung cancer research · 2026Article
- Tumor cell plasticity in non-small cell lung cancer: the role of microRNA and implications for diagnosis, prognosis and treatment.Translational cancer research · 2026Review
- Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies.JTO clinical and research reports · 2026Review
- Synergistic Antitumor Efficacy of Radiofrequency Ablation Combined With TROP2-CAR-T Cells in a Xenograft Mouse Model of Lung Adenocarcinoma.Thoracic cancer · 2026Article
- CAR-T therapy in non-small cell lung cancer: Clinical prospects, potential, and strategies for cardiotoxicity management.Translational oncology · 2026Article
- Mitochondrial niches of residual disease in EGFR-mutant NSCLC: immune-constrained persistence and therapeutic interception.Frontiers in immunology · 2026Review
- Squamous transformation of EGFR-mutant lung adenocarcinoma after EGFR-TKI therapy: clonal continuity, tissue-based diagnosis, and therapeutic evidence gaps.Frontiers in oncology · 2026Review
- TROP2 expression in head and neck squamous cell carcinoma: association with the tumor immune microenvironment and clinical outcome.Frontiers in oncology · 2026Article
- The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.Frontiers in immunology · 2026Review
- Furmonertinib plus pemetrexed in the treatment ofFrontiers in oncology · 2026Article
Corrections and comments
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Authors and funding
37 authors.
Funding
Abstract
EGFR tyrosine kinase inhibitors have dramatically improved outcomes for patients with EGFR-mutated non-small cell lung cancer (NSCLC), but relapse frequently occurs because of drug-tolerant persister (DTP) cells that can evolve and develop diverse mechanisms of drug resistance. In samples from patients with EGFR-mutated NSCLC treated with EGFR tyrosine kinase inhibitors in the neoadjuvant setting, we observed enriched expression of the cell surface protein TROP2, a target of clinically active antibody-drug conjugates (ADC). We confirmed these findings across multiple EGFR-mutated NSCLC cell line and patient-derived xenograft models treated with osimertinib in vivo. Treatment with the TROP2 ADC sacituzumab govitecan at the time of osimertinib-induced minimal residual disease only modestly delayed tumor recurrence in vivo, whereas a single infusion of sacituzumab-based TROP2-directed chimeric antigen receptor (CAR) T cells significantly prolonged relapse-free survival, with evidence of cure. These data highlight the potential of engineering TROP2 CAR T-cell therapy to eliminate EGFR DTPs in patients. SIGNIFICANCE: We provide a rationale for targeting TROP2 in EGFR-mutated NSCLC DTPs. In contrast to TROP2 ADC therapy, targeting of TROP2 with CAR-T cells can eliminate osimertinib-induced DTPs in vivo, revealing the promise of developing novel TROP2-based CAR-T cells to promote durable response and prevent disease relapse in patients.
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Registered trials
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