Tumor blood vessel normalization by prolyl hydroxylase inhibitor repaired sensitivity to chemotherapy in a tumor mouse model

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15054
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Osaka City University (2016); Tottori University (2015)
• Principal Investigator: Tomita Shuhei 大阪市立大学, 大学院医学研究科, 教授 (00263898)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 腫瘍血管 / 低酸素 / PHD阻害剤 / HIF

Outline of Final Research Achievements

In tumor tissue, abnormal blood vessels, which are hyper-permeable and immature, are often formed; these tissues also have irregular vascularization and intravasation. This environment induces resistance to anticancer drugs, which causes an increase in anticancer drug doses, leading to increased side effects. We hypothesized that normalized tumor blood vessels would improve tumor tissue perfusion, resupply nutrition and re-oxygenate the tumor tissue. Chemotherapy would then be more effective and cause a decrease in anticancer drug doses. We report a neovascularization-inducing drug that improved tumor vascular abnormalities, such as low blood flow, blood leakage and abnormal vessel structure. These results could lead to not only an increased chemo-sensitivity and tissue-drug distribution but also an up-regulated efficiency for cancer chemotherapy. This suggests that tumor blood vessel normalization therapy accompanied by angiogenesis may be a novel strategy for cancer therapy.

Free Research Field

血管生物学