Development of new treatment strategy for castration-resistant prostate cancer using a novel nuclear factor kappaB inhibitor

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16816
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Tokyo Medical University
• Principal Investigator: HIRASAWA Yosuke 東京医科大学, 医学部, 助教 (10725310)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 前立腺癌 / 去勢抵抗性前立腺癌 / NFκB / FBP

Outline of Final Research Achievements

The aim of this project is to evaluate the efficacy of the novel NFκB inhibitors for castration-resistant prostate cancer, and it showed significant cytotoxic effects on DU145 cells and also proliferation-inhibiting effect against DU145 cells in subcutaneous tumor bearing mouse. The knockdown of Fuse-Binding Protein (FBP) by transfection method, which is well known as one of significant proteins for proliferation of many kinds of cancer, caused the proliferation-inhibiting effect for prostate cancer. It was showed that both of FBP and NFκB can be a therapeutic target for prostate cancer.

Free Research Field

泌尿器腫瘍学、医学

Academic Significance and Societal Importance of the Research Achievements

去勢抵抗性前立腺癌の予後は不良で、主にアンドロゲン遮断療法が施行されるが、次第にアンドロゲン非依存性増殖能を獲得し、治療抵抗性を示すいわゆる去勢抵抗性前立腺癌となる。ドセタキセルなどタキサン系抗がん剤は有用性が示されているが、予後改善の寄与度はわずか3か月-6か月程度であり、骨髄抑制など有害事象も無視できず新規治療戦略の確立は急務である。今回我々は、FBPとNFκBが共に去勢抵抗性前立腺癌細胞においても治療標的になり得ることを確認し、合成した新規NFκB阻害剤による新たな治療戦略の可能性を見出した。