ArticleOncotarget2016
Acquired nintedanib resistance in FGFR1-driven small cell lung cancer: role of endothelin-A receptor-activated ABCB1 expression.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
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- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancer.Molecular cancer · 2024Review
- Endothelin-1 and Its Role in Cancer and Potential Therapeutic Opportunities.Biomedicines · 2024Review
- Repurposing of the Drug Tezosentan for Cancer Therapy.Current issues in molecular biology · 2023Review
- New Therapeutic Strategy for Overcoming Multidrug Resistance in Cancer Cells with Pyrazolo[3,4-Cancers · 2021Article
- Targeting fibroblast growth factor receptors to combat aggressive ependymoma.Acta neuropathologica · 2021Article
- Review
- FGFR-TKI resistance in cancer: current status and perspectives.Journal of hematology & oncology · 2021Review
- Cerebrospinal fluid penetration of targeted therapeutics in pediatric brain tumor patients.Acta neuropathologica communications · 2020Article
- Repurposing Tyrosine Kinase Inhibitors to Overcome Multidrug Resistance in Cancer: A Focus on Transporters and Lysosomal Sequestration.International journal of molecular sciences · 2020Review
- Potential Therapeutic Strategies for Lung and Breast Cancers through Understanding the Anti-Angiogenesis Resistance Mechanisms.International journal of molecular sciences · 2020Review
- Nanoformulations of anticancer FGFR inhibitors with improved therapeutic index.Nanomedicine : nanotechnology, biology, and medicine · 2018Article
- Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk.Nature communications · 2018Article
- Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer.Journal of experimental & clinical cancer research : CR · 2017Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Genomically amplified fibroblast growth factor receptor 1 (FGFR1) is an oncogenic driver in defined lung cancer subgroups and predicts sensibility against FGFR1 inhibitors in this patient cohort. The FGFR inhibitor nintedanib has recently been approved for treatment of lung adenocarcinoma and is currently evaluated for small cell lung cancer (SCLC). However, tumor recurrence due to development of nintedanib resistance might occur. Hence, we aimed at characterizing the molecular mechanisms underlying acquired nintedanib resistance in FGFR1-driven lung cancer. Chronic nintedanib exposure of the FGFR1-driven SCLC cell line DMS114 (DMS114/NIN) but not of two NSCLC cell lines induced massive overexpression of the multidrug-resistance transporter ABCB1. Indeed, we proved nintedanib to be both substrate and modulator of ABCB1-mediated efflux. Importantly, the oncogenic FGFR1 signaling axis remained active in DMS114/NIN cells while bioinformatic analyses suggested hyperactivation of the endothelin-A receptor (ETAR) signaling axis. Indeed, ETAR inhibition resensitized DMS114/NIN cells against nintedanib by downregulation of ABCB1 expression. PKC and downstream NFκB were identified as major downstream players in ETAR-mediated ABCB1 hyperactivation. Summarizing, ABCB1 needs to be considered as a factor underlying nintedanib resistance. Combination approaches with ETAR antagonists or switching to non-ABCB1 substrate FGFR inhibitors represent innovative strategies to manage nintedanib resistance in lung cancer.
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