The mechanisms that regulate the localization and overexpression of VEGF receptor-2 are promising therapeutic targets in cancer biology.

The vascular endothelial growth factor (VEGF) family has been proposed to be the most important signaling protein family in vessel formation and maturation. VEGF receptor-2 (VEGFR-2) plays an abundant role in the most common forms of cancer. The localization of VEGFR-2 expression is important in cancer pathogenesis; however, so far, little attention has been paid to this phenomenon. Induced cytoplasmic VEGFR-2 transition from the nucleus is associated with poor prognostic cancer stages. Current VEGFR-2-targeted therapy approaches are effective in inhibiting or arresting tumor growth. Moreover, VEGFR-2-targeted therapy was demonstrated to restore the abnormal vasculature in tumors, enhancing their susceptibility toward conventional therapy. Most effects can be found when VEGFR-2-targeted therapy inhibits not only the induced angiogenesis but also the cancer cells that sometimes overexpress VEGFR-2. Nevertheless, we still have little knowledge about the mechanisms that regulate VEGFR-2 expression and how its localization is exactly involved in cancer prognosis. Further research and evaluation of VEGFR-2 regulation and its nuclear transition is necessary to develop more accurate therapeutic strategies to improve the patients' quality of life and their survival.