Mechanism of Androgen Synthesis Activation in Castration-Resistant Prostate Cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09347
• 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: Kyushu University
• Principal Investigator: Shiota Masaki 九州大学, 大学病院, 講師 (20635445)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: アンドロゲン合成 / 去勢抵抗性前立腺癌

Outline of Final Research Achievements

In prostate cancer C4-2 cells, HSD3B1, an androgen synthase, was found to be induced by antiandrogenic agents and suppression of androgen receptor expression. Furthermore, HSD3B1 expression was upregulated in darolutamide-resistant cells, suggesting that HSD3B1 is involved in darolutamide resistance, since suppression of HSD3B1 enhanced sensitivity to darolutamide. In addition, the expression regulator of HSD3B1, NR5A2 (LRH-1), regulates HSD3B1 expression, and inhibition of NR5A2 suppresses HSD3B1 expression and enhances susceptibility to darolutamide.

Free Research Field

泌尿器腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究から、癌におけるアンドロゲン合成におけるNR5A2（LRH-1）が重要な役割を果たしていることが明らかとなった。また、NR5A2/HSD3B1経路は前立腺癌の有望な治療標的であることが示された。今後、本経路を標的とした治療法の開発により、新たな前立腺癌の治療につながることが期待される。