Potentiation of Prostate Cancer Radiotherapy Using Antiangiogenic and Antitumor Therapies

摘要

Various antiangiogenic strategies have proven effective in preclinical tumor models, either as single agents or combined with radiation (RT). The current work aimed to evaluate whether treatment sequencing critically impacts tumor pathophysiological and therapeutic response. Using human prostate tumor models, axitinib, an inhibitor of VEGF receptors, was administered either before or after each daily RT fraction, and pathophysiological changes were monitored. Tumor growth inhibition was equivalent following the two combination schedules. Similar reductions in blood vessel counts were observed with each, tumor hypoxia increased, and pericytes progressively dissociated. These studies illustrate a clear advantage to combining axitinib with fractionated therapy, but argue against an acute radiosensitization or radioprotection of either the tumor cells or tumor vasculature. Instead, post- and pre-RT drug administration serve equally well in supplementing radiotherapeutic response.