Review: Tumor Vasculature and Microenvironment Normalization: A Possible Mechanism of Antiangiogenesis Therapy

摘要

Tumor antiangiogenesis therapy has been in application for more than 30 years; however, its mechanismnremains obscure. An intriguing hypothesis, which has recently gained acceptance, explores the possibilitynthat antiangiogenesis therapy may transiently normalize tumor vasculature and its microenvironment,nthus enhancing chemoradiotherapy efficacy. As the equilibrium between proangiogenesis and antiangiogenesisnfactors is perturbed in the tumor and tips to the former, tumor vasculature tends to exhibit abnormalnstructure and function. Abnormal vasculature is tightly associated with an uncharacteristic microenvironment,nincluding uneven perfusion, hypoxia, and increased interstitial fluid pressure: Thisnmalignant microenvironment hinders the delivery of chemotherapeutics to tumor cells and desensitizesnthe malignant cells to radiation. Antiangiogenesis therapy can reverse the imbalance and transiently normalizenthis microenvironment and gives a new perspective for combining antiangiogenesis therapy andntraditional chemoradiotherapy.