Autophagy, a double-edged sword in anti-angiogenesis therapy

Autophagy is a highly conservative cell behavior to keep the intracellular homeostasis and is frequently activated when cells encounter disgusting conditions, such as nutrition or growth factor deprive, hypoxia and cytotoxic agents. However, the precise role of autophagy under various conditions may be opposite, differ from protect cells survival to promote cells death, and the mechanism of this conditional-dependent role is still unclear. Anti-angiogenesis agents, such as bevacizumab, sorafenib and sunitinib, could reduce tumor microvascular density and increase tumor hypoxia, thus up-regulating autophagy activation of tumor cells, but the function of autophagy induced by anti-angiogenesis agents is still divergent and is considered to play a cytoprotective role in most cases. In this review, we mainly discuss the relationship between anti-angiogenesis therapy-induced hypoxia and autophagy, and pay special attention on the exact role of anti-angiogenesis agents induced autophagy in the process of anti-angiogenesis treatment.