Impact of adjuvant inhibition of vascular endothelial growth factor receptor tyrosine kinases on tumor growth delay and local tumor control after fractionated irradiation in human squamous cell carcinomas in nude mice

Influence of Tumor Cell and Stroma Sensitivity on Tumor Response to Radiation

“…Budach et al found that for large subcurative single doses of radiation, tumor growth delay was greater for the same tumors in SCID versus nude mice, but the doses required for permanent local control did not differ (20). Kozin et al observed that antivascular endothelial growth factor receptor monoclonal antibodies significantly decreased the dose required for local tumor control (21), whereas Zips et al found that adjuvant inhibition of vascular endothelial growth factor receptor kinases increased tumor growth delay, but not local tumor control (22). In the present study, the relatively slower regrowth of irradiated tumors in SCID mice, rather than increased radiation killing of tumor clonogens, accounts for their enhanced growth delay.…”

Atm deletion with dual recombinase technology preferentially radiosensitizes tumor endothelium

“…Although tumors in KP FRT VAtm fl/fl mice were also sensitized to irradiation with 10 fractions of 3 Gy, it is possible that endothelial cell death may increase tumor hypoxia and thereby decrease the efficacy of subsequent fractions of radiation therapy. Furthermore, an increase in growth delay after radiation therapy does not necessarily translate into improved local control (57)(58)(59). To define the contribution of endothelial cells to local control after radiation therapy in this system, future experiments will be required with sarcomas in KP FRT VAtm fl/+ and KP FRT VAtm fl/fl mice using higher doses of radiation and local control as the endpoint.…”

Pathophysiologic Effects of Vascular-Targeting Agents and the Implications for Combination with Conventional Therapies

“…This is true not only for the drug doses and treatment times used but also for the different combination schedules applied with radiation. These include administering the inhibitor during the radiation treatment (54,59,66,(128)(129)(130)(131)(132)(133)(134)(135), before starting the irradiation (46,51,53,58,60), after completing the radiation (47,72,136), or a combination of before, during, and/or after irradiation (49,52,57,61,62,64,65,72,73,128,129,135,(137)(138)(139)(140)(141)(142)(143). Such differences make broad generalizations very difficult.…”