Tumor vasculature and microenvironment normalization: a possible mechanism of antiangiogenesis therapy.

Tumor antiangiogenesis therapy has been in application for more than 30 years; however, its mechanism remains obscure. An intriguing hypothesis, which has recently gained acceptance, explores the possibility that antiangiogenesis therapy may transiently normalize tumor vasculature and its microenvironment, thus enhancing chemoradiotherapy efficacy. As the equilibrium between proangiogenesis and antiangiogenesis factors is perturbed in the tumor and tips to the former, tumor vasculature tends to exhibit abnormal structure and function. Abnormal vasculature is tightly associated with an uncharacteristic microenvironment, including uneven perfusion, hypoxia, and increased interstitial fluid pressure: This malignant microenvironment hinders the delivery of chemotherapeutics to tumor cells and desensitizes the malignant cells to radiation. Antiangiogenesis therapy can reverse the imbalance and transiently normalize this microenvironment and gives a new perspective for combining antiangiogenesis therapy and traditional chemoradiotherapy.