Combination therapy of PARP inhibitor, statin and platinum-containing drug for prostate cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09684
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Gunma University
• Principal Investigator: Sekine Yoshitaka 群馬大学, 大学院医学系研究科, 講師 (00516370)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 前立腺癌 / スタチン / PARP阻害剤 / プラチナ製剤 / 去勢抵抗性前立腺癌

Outline of Final Research Achievements

Our previous study showed that statin decreased many gene expressions, which are related to DNA repair, in androgen independent prostate cancer cells. The combination of statin and PARP inhibitor further enhanced the inhibition of cell proliferation compared with treatment with either treatment alone in androgen independent prostate cancer cells, but triple-drug combination did not enhance the inhibition. The combination of statin and PARP inhibitor further enhanced the expression of γH2AX, which is the marker of DNA damage, compared with treatment with either drug alone in androgen independent prostate cancer cells. These data suggested that the combination of statin and PARP inhibitor can potentially affect castration-resistant prostate cancer growth.

Free Research Field

泌尿器科

Academic Significance and Societal Importance of the Research Achievements

前立腺癌患者は、日本において増加傾向にあり、新規治療の開発は急務である。PARP阻害剤は、去勢抵抗性前立腺癌に対する新規治療薬として注目を浴びているが、現段階では、DNA修復遺伝子変異のある患者のみが治療対象となっている。今回の研究によって、高脂血症薬として使用されているスタチンとの併用により、DNA損傷を引き起こすプラチナ製剤の併用の有無に関わらず、治療に難渋している去勢抵抗性前立腺癌に対して、治療効果がある可能性が示唆された。