Elucidation of the mechanism of resistance to new generation androgen receptor axis-targeted agents by using various patient-derived xenografts of prostate cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06817
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Kyoto University
• Principal Investigator: GOTO TAKAYUKI 京都大学, 医学研究科, 助教 (90806605)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 去勢抵抗性前立腺癌 / xenograft / エンザルタミド抵抗性

Outline of Final Research Achievements

A variety of patient derived xenograft (PDX) models, named KUCaPs, were established using specimens from prostate cancer patients in our laboratory. KUCaPs showed differences in PSA and AR protein expression and gene expression related to castration resistance, and was considered to reflect the clinical heterogeneity of castration resistant prostate cancer (CRPC). We aimed at elucidation of the mechanism of enzalutamide resistance acquisition using KUCaPs, but weak growths and bacterial infections occurred in several lines and they have become impossible to use for experiment. In such a situation, we continued to try to make new KUCaPs from patients resistant to next-generation androgen receptor axis-targeted (ARAT) agents. The newly established model showed resistance to enzalutamide administration.

Free Research Field

泌尿器科

Academic Significance and Societal Importance of the Research Achievements

既存の前立腺癌細胞株では臨床における癌の多様性を十分に反映しておらず、それを用いた研究結果では一部の前立腺癌の性質を探索したにすぎない。ヒトの前立腺癌細胞をそのままマウスに移植して樹立したPDXモデルを多種類用いることが、多様な癌に対応するために重要と考えられる。我々は以前よりこれらのモデルを数種類保持していたが、今回新規アンドロゲン受容体標的治療薬に耐性を示す患者からPDXモデルを作成することに成功した。このモデルではエンザルタミド投薬実験に抵抗性を示しており、これらを解析することで臨床でのエンザルタミド耐性機序の解明に繋がる可能性がある。