Direct Effects of Anti-Angiogenic Therapies on Tumor Cells: VEGF Signaling

Over recent decades anti-angiogenic therapies (AATs) have produced promising results in the treatment of different malignancies. Unfortunately, resistance often develops and patients ultimately relapse. In an attempt to elucidate the causes of recurrence, most studies have focused on tumor responses to hypoxic conditions induced by AAT. However, strategies targeting these mechanisms of resistance are still failing to improve treatments. Furthermore, a potential direct impact of AAT on tumor cells cannot be overlooked. This review provides a novel overview of the different aspects of the tumor cell response to AAT. Conflicting data regarding the nature of this effect are discussed and reconciled, thus providing new insight into the discussion of tumor recurrence despite AAT.