The effects of PARP inhibitors on tumor metastasis via blood vessels

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20711
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: The University of Tokushima
• Principal Investigator: IMANISHI Masaki 徳島大学, 大学院医歯薬学研究部(薬学域), 助教 (00734344)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 血行性がん転移 / 抗がん剤 / 血管内皮細胞

Outline of Final Research Achievements

In the present study, we investigated the mechanisms of chemotherapy-induced tumor metastasis via endothelial cell (EC)-derived poly ADP-ribose polymerase (PARP) activation to find possibilities that PARP inhibitors can be applied also as inhibitors against tumor metastasis during cancer therapies. We found that cisplatin (CDDP) induced PARP activation in ECs, CDDP pre-administration induced melanoma tumor cell metastasis and a PARP inhibitor, olaparib administration suppressed its effect in a mouse model.

Free Research Field

循環薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究により、抗がん剤によるEC由来PARP活性化を介した血行性がん転移促進機序が解明されることにより、(1)すでに臨床で使用されているPARP阻害薬の血行性がん転移予防への適応拡大の可能性、(2)将来の血行性がん転移制御も考慮した効率的がん治療戦略の開発、に向けて一石を投じることが可能となる。