Pressing questions in this category are: (1) are the GBM tumors in patients that have failed bevacizumab or other anti-angiogenic therapy avascular, or are the tumors co-opting the existing blood vessels to obtain the oxygen and nutrients needed?, (2) is the angiopoietin signaling pathway driving a blood vessel co-option process in human GBM that have failed therapy with a VEGF inhibitor or other anti-angiogenic agent?, and (3) do cancer stem cells (or glioma stem cells) promote angiogenesis in malignant gliomas and could we target them specifically with novel therapy? The gene discussed is VEGFA; the disease is central nervous system cancer.