ArticleBritish journal of cancer2019
Anti-angiogenic effects of crenolanib are mediated by mitotic modulation independently of PDGFR expression.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Stromal PDGFR-beta expression is a prognostic factor in high-grade serous ovarian cancer patients but is it also predictive for response to antiangiogenic treatment?Journal of cancer research and clinical oncology · 2025Article
- Drugs in the GIST Field (Therapeutic Targets and Clinical Trial Staging).Current drug delivery · 2024Article
- Microvascular Experimentation in the Chick Chorioallantoic Membrane as a Model for Screening Angiogenic Agents including from Gene-Modified Cells.International journal of molecular sciences · 2021Review
- Crosstalk between Cancer Cells and Fibroblasts for the Production of Monocyte Chemoattractant Protein-1 in the Murine 4T1 Breast Cancer.Current issues in molecular biology · 2021Article
- Forcing dividing cancer cells to die; low-dose drug combinations to prevent spindle pole clustering.Apoptosis : an international journal on programmed cell death · 2021Review
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- Identification of low-dose multidrug combinations for sunitinib-naive and pre-treated renal cell carcinoma.British journal of cancer · 2020Article
- Antiangiogenesis Efficacy of Ethanol Extract fromEvidence-based complementary and alternative medicine : eCAM · 2020Article
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Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCrenolanib is a tyrosine kinase inhibitor targeting PDGFR-α, PDGFR-β and Fms related tyrosine kinase-3 (FLT3) that is currently evaluated in several clinical trials. Although platelet-derived growth factor receptor (PDGFR) signalling pathway is believed to play an important role in angiogenesis and maintenance of functional vasculature, we here demonstrate a direct angiostatic activity of crenolanib independently of PDGFR signalling.
methodsThe activity of crenolanib on cell viability, migration, sprouting, apoptosis and mitosis was assessed in endothelial cells, tumour cells and fibroblasts. Alterations in cell morphology were determined by immunofluorescence experiments. Flow-cytometry analysis and mRNA expression profiles were used to investigate cell differentiation. In vivo efficacy was investigated in human ovarian carcinoma implanted on the chicken chorioallantoic membrane (CAM).
resultsCrenolanib was found to inhibit endothelial cell viability, migration and sprout length, and induced apoptosis independently of PDGFR expression. Treated cells showed altered actin arrangement and nuclear aberrations. Mitosis was affected at several levels including mitosis entry and centrosome clustering. Crenolanib suppressed human ovarian carcinoma tumour growth and angiogenesis in the CAM model.
conclusionsThe PDGFR/FLT3 inhibitor crenolanib targets angiogenesis and inhibits tumour growth in vivo unrelated to PDGFR expression. Based on our findings, we suggest a broad mechanism of action of crenolanib.
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