EGFR-mutant transformed small cell lung cancer harbors intratumoral heterogeneity targetable with MEK inhibitor combination therapy.
1/5 보강
Small cell lung cancer (SCLC) transformation is an incompletely characterized mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant cancers,
APA
Ogino A, Vajdi A, et al. (2026). EGFR-mutant transformed small cell lung cancer harbors intratumoral heterogeneity targetable with MEK inhibitor combination therapy.. JCI insight, 11(2). https://doi.org/10.1172/jci.insight.197008
MLA
Ogino A, et al.. "EGFR-mutant transformed small cell lung cancer harbors intratumoral heterogeneity targetable with MEK inhibitor combination therapy.." JCI insight, vol. 11, no. 2, 2026.
PMID
41574603 ↗
Abstract 한글 요약
Small cell lung cancer (SCLC) transformation is an incompletely characterized mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant cancers, limiting development of optimal treatment approaches. Through single-cell RNA sequencing of malignant pleural effusions from patients who underwent SCLC transformation, we identified heterogeneity and diversity, including distinct neuroendocrine (NE) and mesenchymal non-NE cancer cell subsets, which were maintained in patient-derived cell lines. We demonstrate that EZH2 regulates EGFR expression in NE cells where EGFR expression is silenced at baseline. Although neither epigenetic derepression nor exogenous overexpression of mutant EGFR sensitized the cells to EGFR inhibition, non-NE cells exhibited selective sensitivity to MEK inhibitors. Combined MEK inhibitor and chemotherapy effectively inhibited growth of both NE and non-NE cells in vitro and in vivo. Our findings demonstrate that EGFR-mutant SCLC is composed of mixed cell states with distinct therapeutic vulnerabilities and offer a therapeutic strategy to target tumor heterogeneity in highly plastic and treatment-resistant malignancies such as transformed SCLC.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Humans
- Small Cell Lung Carcinoma
- ErbB Receptors
- Lung Neoplasms
- Protein Kinase Inhibitors
- Animals
- Mice
- Mutation
- Cell Line
- Tumor
- Drug Resistance
- Neoplasm
- Xenograft Model Antitumor Assays
- Female
- Single-Cell Analysis
- Male
- Antineoplastic Combined Chemotherapy Protocols
- Cell Transformation
- Neoplastic
- Cell biology
- Drug therapy
- Lung cancer
- Oncology
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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