ArticleMolecular cancer therapeutics2014
Acquired resistance to dasatinib in lung cancer cell lines conferred by DDR2 gatekeeper mutation and NF1 loss.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
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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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology.Cancer metastasis reviews · 2022Pooled it
- Efficacy and safety of trametinib in Japanese patients with advanced biliary tract cancers refractory to gemcitabine.Cancer science · 2018Trial
- Discoidin Domain Receptor 2 Contributes to Breast Cancer Progression and Chemoresistance by Interacting with Collagen Type I.Cancers · 2024Article
- Investigation of Cell Mechanics and Migration on DDR2-Expressing Neuroblastoma Cell Line.Life (Basel, Switzerland) · 2024Article
- Landscape of targeted therapies for lung squamous cell carcinoma.Frontiers in oncology · 2024Review
- N-acetylcysteine overcomes NF1 loss-driven resistance to PI3Kα inhibition in breast cancer.Cell reports. Medicine · 2023Article
- Focusing on discoidin domain receptors in premalignant and malignant liver diseases.Frontiers in oncology · 2023Review
- Resistance to DNA repair inhibitors in cancer.Molecular oncology · 2022Review
- Potential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas.Cancers · 2021Article
- The Yin and Yang of Discoidin Domain Receptors (DDRs): Implications in Tumor Growth and Metastasis Development.Cancers · 2021Review
- Review
- Advancement in research and therapy ofCancer cell international · 2020Review
- Identification of biomarkers and their functions in dasatinib-resistant pancreatic cancer using bioinformatics analysis.Oncology letters · 2019Article
- Targeting DDR2 enhances tumor response to anti-PD-1 immunotherapy.Science advances · 2019Article
- Neurofibromin 1 expression is negatively correlated with malignancy and prognosis of epithelial ovarian cancer.International journal of clinical and experimental pathology · 2019Article
- DDR1 and MT1-MMP Expression Levels Are Determinant for Triggering BIK-Mediated Apoptosis by 3D Type I Collagen Matrix in Invasive Basal-Like Breast Carcinoma Cells.Frontiers in pharmacology · 2019Article
- Tipifarnib Inhibits HRAS-Driven Dedifferentiated Thyroid Cancers.Cancer research · 2018Article
- Inhibition of tumor-microenvironment interaction and tumor invasion by small-molecule allosteric inhibitor of DDR2 extracellular domain.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- CAPN1 is a novel binding partner and regulator of the tumor suppressor NF1 in melanoma.Oncotarget · 2018Article
- Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
The treatment of non-small cell lung cancer has evolved dramatically over the past decade with the adoption of widespread use of effective targeted therapies in patients with distinct molecular alterations. In lung squamous cell carcinoma (lung SqCC), recent studies have suggested that DDR2 mutations are a biomarker for therapeutic response to dasatinib and clinical trials are underway testing this hypothesis. Although targeted therapeutics are typically quite effective as initial therapy for patients with lung cancer, nearly all patients develop resistance with long-term exposure to targeted drugs. Here, we use DDR2-dependent lung cancer cell lines to model acquired resistance to dasatinib therapy. We perform targeted exome sequencing to identify two distinct mechanisms of acquired resistance: acquisition of the T654I gatekeeper mutation in DDR2 and loss of NF1. We show that NF1 loss activates a bypass pathway, which confers ERK dependency downstream of RAS activation. These results indicate that acquired resistance to dasatinib can occur via both second-site mutations in DDR2 and by activation of bypass pathways. These data may help to anticipate mechanisms of resistance that may be identified in upcoming clinical trials of anti-DDR2 therapy in lung cancer and suggest strategies to overcome resistance.
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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 OpenQuestion graph.