2022 Fiscal Year Final Research Report
Development of opitimal drug screening using 3D in vitro prostate cancer organoid
| Project/Area Number |
20H03806
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
萩中 淳 武庫川女子大学, バイオサイエンス研究所, 教授 (20164759)
塩田 真己 九州大学, 大学病院, 講師 (20635445)
平田 寛 山口大学, 医学部附属病院, 助教 (40781307)
清木 誠 山口大学, 大学院医学系研究科, 教授 (50226619)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | オルガノイド / CRPC / 薬剤感受性試験 / アビラテロン |
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| Outline of Final Research Achievements |
(1) Development of in vitro models reflecting bone microenvironment and primary tumor microenvironment: As a result of conducting sensitivity tests to various new androgen receptor blockers (ARATs) using the above model. Both models showed IC50 values of darolutamide was lower than enzalutamide, and apalutamide. (2) Establish of prostate cancer-derived organoids: We have succeeded in creating 10 strains of organoids (including 2 GFP-induced strains) from prostate cancer surgical specimens. (3) Phase II clinical trial in combination with abiraterone and dutasteride for patients with castration-resistant prostate cancer.
The primary endpoint of less than 50% PSA reduction was observed in 18 out of 21 patients (85.7%) with a median follow-up of 15.4 months. There were no adverse events of Grade 3 or higher. Higher 3-keto-5α-abiraterone concentrations were associated with shorter TTF in combination therapy. TTF was prolonged in patients with homozygous wild-type HSD3B1.
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| Free Research Field |
泌尿器科
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で開発した骨微小環境および原発巣微小環境モデルは、ARATs薬剤スクリーニングとして有用であり、薬剤選択の一助となりうる。アビラテロン、デュタステリド併用第II相臨床試験はアビラテロン代謝経路を考慮した理論通りの高い治療効果を示し、代謝中間体（Δ4-アビラテロン、3-ケト-5α-アビラテロン）の推移と臨床効果との相関を証明したことは学術的意義が高い。さらに同代謝酵素の遺伝多型を調べることにより、併用療法がもっとも有効な患者を選択することが可能であることを臨床的に証明したことは、同併用療法の臨床応用に向けた社会的意義は極めて高いと思われる。
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