VEGFA and glioblastoma: Both VEGF and YKL-40 had synergistic effects on tumor angiogenesis, however persistent blockage of VEGF led to upregulation of YKL-40, supporting that glioblastoma eventually develop VEGF-independent pathways of tumor vascularization (Figure 1); this may be one of the mechanisms that explains why glioblastoma always becomes resistant to anti-VEGF treatment such as bevacizumab.