Effects of vascular normalization on progression of prostate cancer and therapeutic efficacy

Abstract

Targeting VEGF pathway suppresses tumor progression by starving tumor cells though blocking tumor blood supply but hypoxia induced by blocking vessels aggravates tumor progression and induces metastatic potential and treatment resistance. Tumor vessels are typically leaky, dilated, Saccular, and tortuous. These abnormal blood vessels result in a hostile tumor microenvironment characterized by hypoxia, low pH and high interstitial fluid pressure. Impaired blood flow interferes drug delivery to solid tumor and impedes therapeutic efficacy of cancer agents. Here, we investigated role of vascular normalization in cancer progression and delivery of chemotherapeutic agent in prostate cancer. Normalization of vasculature by reducing vascular leakiness reduced hypoxic phenotype and improved vascular perfusion in the PC-3 xenografts. It also increased concentration of chemotherapeutic agent. Our study demonstrated that direct normalization of vasculature by vascular normalizing agent could provide a strategy to prostate cancer and the efficacy of chemotherapy.