Development of novel ovarian cancer therapy targeting angiogenesis and immune escape by the vasohibin family

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K11294
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Jichi Medical University
• Principal Investigator: Saga Yasushi 自治医科大学, 医学部, 准教授 (70360071)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: バソヒビン2 / 卵巣がん / パクリタキセル / シスプラチン

Outline of Final Research Achievements

Vasohibin-2 (VASH2) is expressed in many cancer cells to accelerate tumor angiogenesis and tumor progression. Recent years, it has been reported that VASH2 has a tubulin carboxypeptidase activity related to microtubule functions. Paclitaxel (PTX), a key drug for ovarian cancer therapy, acts as an inhibitor of microtubule depolymerization, which may show some interactions with VASH2. We have established 4 VASH2 knocked out ovarian cancer cell lines by CRISPR/Cas9 genome editing system to examine the intracellular tubulin detyrosination status and the PTX chemosensitivity. The knockout of VASH2 significantly increased PTX chemosensitivity, whereas it did not affect chemosensitivity to cisplatin in all 4 knocked out cell lines. From these results, in the ovarian cancer treatment strategies targeting VASH2, not only known angiogenesis inhibition but also increasing PTX chemosensitivity can be expected.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

バソヒビン2を標的とした卵巣がん新規治療法の開発を目指して研究を行っている。今回の検討結果から、バソヒビン2のノックアウトは、卵巣がん初回多剤併用化学療法の第一選択であるパクリタキセル-シスプラチン併用療法に用いられる抗がん剤であるパクリタキセルの感受性を増強させ、一方、シスプラチンの感受性には影響を与えないことが明らかとなった。この知見からバソヒビン2を標的とした卵巣がん新規治療法は従来の多剤併用化学療法との同時施行により、より良い治療効果が得られる可能性が示唆され、ひいては卵巣がんの予後改善につながる可能性がある。