The ability to recruit and expand new blood vessels is an essential component of tumour growth. Hence, the main goal of this study was to determine whether we could prevent the growth of bone metastases by blocking angiogenesis via the use of the vascular disrupting agent (VDA), DMXAA, either alone, or used in combination with the pan-PI3K inhibitor, GDC-0941. DMXAA, an agent of the flavonoid class, has been shown to disrupt the tumour vasculature in a number of model systems by selectively inducing apoptosis in tumour vascular endothelial cells. Since the PI3K/Akt pathway has been shown to increase cell survival, growth, and proliferation, we hypothesized that by inhibiting a major anti-apoptotic mechanism, a PI3K inhibitor, we would be able to increase the anti-vascular effects of a VDA within bone metastasis xenografts. Contrary to what we expected, DMXAA, either alone or in combination with GDC-0941, had no statistically significant on bioluminescence of established metastases while bioluminescence of subcutaneous tumours was severely affected. Our studies provide a possible explanation for the failure of DMXAA in human clinical trials.