Development of a multi-targeted castration-resistant prostate cancer drug for clinical application

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11151
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: Endo Satoshi 岐阜薬科大学, 薬学部, 准教授 (60433207)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 去勢抵抗性前立腺癌 / AKR1C3 / 抗癌剤耐性克服

Outline of Final Research Achievements

To improve the treatment of castration-resistant prostate cancer (CRPC), we developed potent and specific inhibitors of AKR1C3, a novel target of prostate cancer. We also succeeded in X-ray crystallographic analysis of the enzyme-coenzyme-inhibitor tertiary complex and clarified the binding mode the inhibitors with AKR1C3. In addition, the AKR1C3 inhibitors exhibited potentiating effects on the anticancer activity of the existing CRPC agents and overcoming effects against the resistance, suggesting that the novel AKR1C3 inihibitors may be an effective novel adjuvant drugs for overcoming the resistance in CRPC agents-resistant prostate cancer.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

前立腺癌は10年生存率が95%を超える比較的予後の良い癌として知られるが、世界的に罹患率の高い癌であり、一般的には欧米人に多いとされてきたが、本邦でも高齢化、食の欧米化などを背景に急速に患者数が増加し、最新がん統計では胃癌に次いで2番目に高いがん罹患率を示す。また、内分泌療法の長期継続によって治療が困難な去勢抵抗性前立腺癌（CRPC）へと移行することが問題である。本研究成果は、CRPC患者における生活の質の向上を目指し、既存治療薬の効果の最大化に向けた有益な知見を与えることが期待される。