Among the numerous endogenous promoters of angiogenesis, vascular endothelia growth factor (VEGF) plays
a leading role in angiogenesis, which has huge impact on proliferation, survival, migration and permeability of tumor
cells. VEGF signal system also becomes remarkable anticancer targets, including VEGF, vascular endothelia growth factor
receptor (VEGFR), and VEGF downstream signal pathways. So far, there has been many clinical or approved anticancer
drugs that directly or indireactly interfere with VEGF signal system applied in the treatment of various tumors and
other diseases associated with pathological angiogenesis. Various kinds of antiangiogenic agents which inhibit VEGF and
VEGFR have been developed and discovered gradually, including antibodies, ribozymes and small molecule inhibitors.
Meanwhile, the investigation into antiangiogenic agents which block certain signal proteins of VEGF downstream signal
pathways attracts the attention of medicinal chemists and enriches the application of antiangiogenic agents. This review
will interpret the mysterious VEGF signal system from its molecular structure and probe to the mechanism of the combination
of VEGF and its receptors. Furthermore, the detail of VEGF signal pathways will be introduced comprehensively
and methodically. In addition, some up-to-date clinical or approved anticancer agents will be clearly tabulated. The binding
modes of different kinase inhibitors will be used to explain the SAR of the small molecule inhibitors. Finally, in order
to make the readers master VEGF signal system completely, some novel targets and inhibitors which block the downstream
signal pathways of VEGF are plainly stated.