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Masaki Shiota Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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Satoshi Endo United Graduate School of Medical Information Sciences, Gifu University, Gifu, Japan
Center for One Medicine Innovative Translational Research (COMIT), Gifu University, Gifu, Japan

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Shigehiro Tsukahara Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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Tokiyoshi Tanegashima Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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Satoshi Kobayashi Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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Takashi Matsumoto Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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Masatoshi Eto Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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Androgen receptor signaling is crucial for the development of treatment resistance in prostate cancer. Among steroidogenic enzymes, 3β-hydroxysteroid dehydrogenases (3βHSDs) play critical roles in extragonadal androgen synthesis, especially 3βHSD1. Increased expression of 3βHSDs is observed in castration-resistant prostate cancer tumors compared with primary prostate tumors, indicating their involvement in castration resistance. Recent studies link 3βHSD1 to resistance to androgen receptor signaling inhibitors. The regulation of 3βHSD1 expression involves various factors, including transcription factors, microenvironmental influences, and posttranscriptional modifications. Additionally, the clinical significance of HSD3B1 genotypes, particularly the rs1047303 variant, has been extensively studied. The impact of HSD3B1 genotypes on treatment outcomes varies according to the therapy administered, suggesting the potential of HSD3B1 genotyping for personalized medicine. Targeting 3βHSDs may be a promising strategy for prostate cancer management. Overall, understanding the roles of 3βHSDs and their genetic variations may enable the development and optimization of novel treatments for prostate cancer.

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