ArticleOncoTargets and therapy2015
Crosstalk with cancer-associated fibroblasts induces resistance of non-small cell lung cancer cells to epidermal growth factor receptor tyrosine kinase inhibition.
Article in OncoTargets and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- Targeting CAF-specific metabolic pathways in breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Risk factors and management of lung cancer in idiopathic pulmonary fibrosis: A comprehensive review.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2025Article
- Overcoming EGFR-TKI resistance by targeting the tumor microenvironment.Chinese medical journal pulmonary and critical care medicine · 2024Review
- Article
- Features of tumor-microenvironment images predict targeted therapy survival benefit in patients with EGFR-mutant lung cancer.The Journal of clinical investigation · 2023Article
- Therapeutic Targeting of Cancer-Associated Fibroblasts in the Non-Small Cell Lung Cancer Tumor Microenvironment.Cancers · 2023Review
- Cancer-associated fibroblasts in nonsmall cell lung cancer: From molecular mechanisms to clinical implications.International journal of cancer · 2022Review
- In Vitro Effect of Δ9-Tetrahydrocannabinol and Cannabidiol on Cancer-Associated Fibroblasts Isolated from Lung Cancer.International journal of molecular sciences · 2022Article
- Cancer-associated fibroblasts and resistance to anticancer therapies: status, mechanisms, and countermeasures.Cancer cell international · 2022Review
- Natural Compounds Targeting Cancer-Associated Fibroblasts against Digestive System Tumor Progression: Therapeutic Insights.Biomedicines · 2022Review
- Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances.Frontiers in oncology · 2022Review
- Review
- [SP13786 Inhibits the Migration and Invasion of Lung Adenocarcinoma Cell A549 by Supressing Stat3-EMT via CAFs Exosomes].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Article
- Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer.Signal transduction and targeted therapy · 2021Review
- Role of cancer-associated fibroblasts in the resistance to antitumor therapy, and their potential therapeutic mechanisms in non-small cell lung cancer.Oncology letters · 2021Review
- Long non-coding RNAs in lung cancer: implications for lineage plasticity-mediated TKI resistance.Cellular and molecular life sciences : CMLS · 2021Review
- Cancer-Associated Fibroblasts as a Common Orchestrator of Therapy Resistance in Lung and Pancreatic Cancer.Cancers · 2021Review
- M2 macrophages reduce the effect of gefitinib by activating AKT/mTOR in gefitinib-resistant cell lines HCC827/GR.Thoracic cancer · 2020Article
- Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics.Frontiers in oncology · 2020Review
- Characterization and printability of Sodium alginate -Gelatin hydrogel for bioprinting NSCLC co-culture.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although lung cancers with activating mutations in the epidermal growth factor receptor (EGFR) are highly sensitive to selective EGFR tyrosine kinase inhibitors (TKIs), these tumors invariably develop acquired drug resistance. Host stromal cells have been found to have a considerable effect on the sensitivity of cancer cells to EGFR TKIs. Little is known, however, about the signaling mechanisms through which stromal cells contribute to the response to EGFR TKI in non-small cell lung cancer. This work examined the role of hedgehog signaling in cancer-associated fibroblast (CAF)-mediated resistance of lung cancer cells to the EGFR TKI erlotinib. PC9 cells, non-small cell lung cancer cells with EGFR-activating mutations, became resistant to the EGFR TKI erlotinib when cocultured in vitro with CAFs. Polymerase chain reaction and immunocytochemical assays showed that CAFs induced epithelial to mesenchymal transition phenotype in PC9 cells, with an associated change in the expression of epithelial to mesenchymal transition marker proteins including vimentin. Importantly, CAFs induce upregulation of the 7-transmembrane protein smoothened, the central signal transducer of hedgehog, suggesting that the hedgehog signaling pathway is active in CAF-mediated drug resistance. Indeed, downregulation of smoothened activity with the smoothened antagonist cyclopamine induces remodeling of the actin cytoskeleton independently of Gli-mediated transcriptional activity in PC9 cells. These findings indicate that crosstalk with CAFs plays a critical role in resistance of lung cancer to EGFR TKIs through induction of the epithelial to mesenchymal transition and may be an ideal therapeutic target in lung cancer.
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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.