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.
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.
Original language | English |
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Article number | 30038 |
Pages (from-to) | 1-10 |
Number of pages | 10 |
Journal | Scientific Reports |
Volume | 6 |
DOIs | |
Publication status | Published - 22 Jul 2016 |
Bibliographical note
AcknowledgementsThe authors would like to thank Maria Kisakyamaria and Scott McMenemy for preliminary experimental data. This work was supported by a Wellcome Trust-NIH PhD Studentship awarded to SB, WDF and NV (Grant number 098252/Z/12/Z). This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government.
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Neil Vargesson
- School of Medicine, Medical Sciences & Nutrition, Molecular and Cellular Function
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Chair in Developmental Biology
- School of Medicine, Medical Sciences & Nutrition, MRC/Versus Arthritis Centre for Musculoskeletal Health and Work
- Institute of Medical Sciences
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Centre for Arthritis and Musculoskeletal Health (ACAMH)
Person: Academic