A new treatment strategy targeting to DNA repair pathway of castration resistant prostate cancer

• Project/Area Number: 15K20108
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Keio University
• Principal Investigator: Kobayashi Hiroaki 慶應義塾大学, 医学部(信濃町), 助教 (10598428)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 去勢抵抗性前立腺癌 / ドセタキセル抵抗性 / PARP阻害剤 / DNA修復機構 / 合成致死 / アポトーシス / DNA修復経路

Outline of Final Research Achievements

In this study, we explored the efficacy of a PARP inhibitor for docetaxel resistant prostate cancer cell line: C4-2AT6. C4-2AT6 cells revealed combined administration of PARP inhibitor and docetaxel had a significant and synergistically high apoptosis inducing effect. In a castrated mice xenograft model, combined PARP inhibitor and docetaxel also showed high anti-tumor effect. These results suggested that inhibition of DNA repair pathway was able to overcome docetaxel resistance in human docetaxel resistant prostate cancer.