Interaction of angiogenesis inhibition and radiotherapy
Study on the interaction between angiogenesis inhibition and radiotherapy
Thijssen VLJL, Castricum K, Senan S, Griffioen AW, Verheul HM, Slotman B
Depts. of Radiotherapy and Medical Oncology, VU University Medical Center
The main purpose of this proposal is to study the interaction between anti-angiogenesis therapy and radiotherapy in order to improve therapeutic strategies in cancer patients.
For several endothelial cell lines and multiple tumor cell lines, the dose-response curves after mono-therapy with either angiogenesis inhibitors or radiation have been generated. It appears that the endothelial cells are less sensitive to radiotherapy compared to tumor cells. Especially the primary HUVEC are relatively resistant to radiotherapy. Moreover, culture supernatants of irradiated tumor cells induce more endothelial cell proliferation as compared to untreated tumor cells. This suggests that radiotherapy alone induces a pro-angiogenesis response.
To study the effects of combination therapy on angiogenesis in vivo, experiments have been performed in chicken eggs. Using this modified chicken chorioallantoic membrane assay, small but significant changes in vascular development can be observed after radiotherapy with intermediate dose (2-5 Gy). Additional experiments identified a 3-day window which can be used to apply anti-angiogenesis therapy before radiation therapy starts. Experiments to study the effects of combination therapy in this model have been initiated