PUBLICATION
Shared mechanism of teratogenicity of anti-angiogenic drugs identified in the chicken embryo model
- Authors
- Beedie, S.L., Mahony, C., Walker, H.M., Chau, C.H., Figg, W.D., Vargesson, N.
- ID
- ZDB-PUB-160725-37
- Date
- 2016
- Source
- Scientific Reports 6: 30038 (Journal)
- Registered Authors
- Mahony, Christopher
- Keywords
- Angiogenesis, Embryology
- MeSH Terms
-
- Angiogenesis Inhibitors/adverse effects*
- Animals
- Cells, Cultured
- Chick Embryo
- Dose-Response Relationship, Drug
- Humans
- Teratogenesis*
- Teratogens/pharmacology*
- Zebrafish/embryology
- PubMed
- 27443489 Full text @ Sci. Rep.
Citation
Beedie, S.L., Mahony, C., Walker, H.M., Chau, C.H., Figg, W.D., Vargesson, N. (2016) Shared mechanism of teratogenicity of anti-angiogenic drugs identified in the chicken embryo model. Scientific Reports. 6:30038.
Abstract
Angiogenesis, the formation of new blood vessels, is essential for tumor growth, stabilization and progression. Angiogenesis inhibitors are now widely used in the clinic; however, there are relatively few published studies on the mechanism of their presumed teratogenic effects. To address this issue, we screened a variety of angiogenesis inhibitors in developing zebrafish and chicken embryo models to assess for developmental defects and potential teratogenic effects. We confirmed previous reports that sunitinib, sorafenib and TNP-470 are teratogenic and demonstrate that axitinib, pazopanib, vandetanib, and everolimus are also teratogens in these models. A dose response study identified the drugs inhibit HUVEC cell proliferation in vitro, and also target the developing blood vessels of embryos in vivo. This provides further evidence for the potential risk of fetal toxicity when using these drugs in a clinical setting, and emphasizes the importance of the development and maintenance of the vasculature in the embryo. We conclude that angiogenesis inhibitors, regardless of the molecular target, are teratogenic when exposed to chicken embryos.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping