Importance of 3β-hydroxysteroid dehydrogenases and their clinical use in prostate cancer

in Endocrine-Related Cancer
Authors:
Masaki Shiota Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Search for other papers by Masaki Shiota in
Current site
Google Scholar
PubMed Close
https://orcid.org/0000-0002-3306-4858
,
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

Search for other papers by Satoshi Endo in
Current site
Google Scholar
PubMed Close
,
Shigehiro Tsukahara Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Search for other papers by Shigehiro Tsukahara in
Current site
Google Scholar
PubMed Close
,
Tokiyoshi Tanegashima Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Search for other papers by Tokiyoshi Tanegashima in
Current site
Google Scholar
PubMed Close
,
Satoshi Kobayashi Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Search for other papers by Satoshi Kobayashi in
Current site
Google Scholar
PubMed Close
,
Takashi Matsumoto Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Search for other papers by Takashi Matsumoto in
Current site
Google Scholar
PubMed Close
, and
Masatoshi Eto Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Search for other papers by Masatoshi Eto in
Current site
Google Scholar
PubMed Close

Correspondence should be addressed to M Shiota: shiota.masaki.101@m.kyushu-u.ac.jp
DOI:
https://doi.org/10.1530/ERC-24-0023
Volume/Issue:
Volume 31: Issue 7
Article Type:
Review Article
Article ID:
e240023
Online Publication Date:
20 May 2024
Copyright:
© the author(s) 2024
Restricted access
Rent on DeepDyve

Sign up for journal news

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.

Endocrine-Related Cancer is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 79 79 3
PDF Downloads 109 109 3

 

  • Collapse
  • Expand
Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2024
Article ID:
e240023
Received Date:
02 Feb 2024
Accepted Date:
29 Apr 2024
Print Publication Date:
01 Jul 2024
Online Publication Date:
20 May 2024
Keywords:
androgen; ARSI; CRPC; HSD3B1; steroidogenesis

  • Agarwal N, Hahn AW, Gill DM, Farnham JM, Poole AI & & Cannon-Albright L 2017 Independent validation of effect of HSD3B1 genotype on response to androgen-deprivation therapy in prostate cancer. JAMA Oncology 3 856–857. (https://doi.org/10.1001/jamaoncol.2017.0147)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Almassi N, Reichard C, Li J, Russell C, Perry J, Ryan CJ, Friedlander T & & Sharifi N 2018 HSD3B1 and response to a nonsteroidal CYP17A1 inhibitor in castration-resistant prostate cancer. JAMA Oncology 4 554–557. (https://doi.org/10.1001/jamaoncol.2017.3159)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Alyamani M, Emamekhoo H, Park S, Taylor J, Almassi N, Upadhyay S, Tyler A, Berk MP, Hu B & Hwang TH, et al.2018 HSD3B1(1245A>C) variant regulates dueling abiraterone metabolite effects in prostate cancer. Journal of Clinical Investigation 128 3333–3340. (https://doi.org/10.1172/JCI98319)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Amrousy YM, Haffez H, Abdou DM & & Atya HB 2022 Role of single nucleotide polymorphisms of the HSD3B1 gene (rs6203 and rs33937873) in the prediction of prostate cancer risk. Molecular Medicine Reports 26 271. (https://doi.org/10.3892/mmr.2022.12787)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Attard G, Reid AHM, Yap TA, Raynaud F, Dowsett M, Settatree S, Barrett M, Parker C, Martins V & Folkerd E, et al.2008 Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. Journal of Clinical Oncology 26 4563–4571. (https://doi.org/10.1200/JCO.2007.15.9749)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Berndt SI, Chatterjee N, Huang WY, Chanock SJ, Welch R, Crawford ED & & Hayes RB 2007 Variant in sex hormone-binding globulin gene and the risk of prostate cancer. Cancer Epidemiology, Biomarkers and Prevention 16 165–168. (https://doi.org/10.1158/1055-9965.EPI-06-0689)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Beuten J, Gelfond JAL, Franke JL, Weldon KS, Crandall AC, Johnson-Pais TL, Thompson IM & & Leach RJ 2009 Single and multigenic analysis of the association between variants in 12 steroid hormone metabolism genes and risk of prostate cancer. Cancer Epidemiology, Biomarkers and Prevention 18 1869–1880. (https://doi.org/10.1158/1055-9965.EPI-09-0076)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Blas L, Shiota M & & Eto M 2022 Current status and future perspective on the management of metastatic castration-sensitive prostate cancer. Cancer Treatment and Research Communications 32 100606. (https://doi.org/10.1016/j.ctarc.2022.100606)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Boibessot C & & Toren P 2018 Sex steroids in the tumor microenvironment and prostate cancer progression. Endocrine-Related Cancer 25 R179–R196. (https://doi.org/10.1530/ERC-17-0493)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bonkhoff H 2018 Estrogen receptor signaling in prostate cancer: implications for carcinogenesis and tumor progression. Prostate 78 2–10. (https://doi.org/10.1002/pros.23446)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Buck SAJ, Meertens M, van Ooijen FMF, Oomen-de Hoop E, de Jonge E, Coenen MJH, Bergman AM, Koolen SLW, de Wit R & Huitema ADR, et al.2023 A common germline variant in CYP11B1 is associated with adverse clinical outcome of treatment with abiraterone or enzalutamide. Biomedicine and Pharmacotherapy 169 115890. (https://doi.org/10.1016/j.biopha.2023.115890)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chang BL, Zheng SL, Hawkins GA, Isaacs SD, Wiley KE, Turner A, Carpten JD, Bleecker ER, Walsh PC & Trent JM, et al.2002 Joint effect of HSD3B1 and HSD3B2 genes is associated with hereditary and sporadic prostate cancer susceptibility. Cancer Research 62 1784–1789.

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chang KH, Li R, Kuri B, Lotan Y, Roehrborn CG, Liu J, Vessella R, Nelson PS, Kapur P & Guo X, et al.2013 A gain-of-function mutation in DHT synthesis in castration-resistant prostate cancer. Cell 154 1074–1084. (https://doi.org/10.1016/j.cell.2013.07.029)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chen R, Yu Y & & Dong X 2017 Progesterone receptor in the prostate: a potential suppressor for benign prostatic hyperplasia and prostate cancer. Journal of Steroid Biochemistry and Molecular Biology 166 91–96. (https://doi.org/10.1016/j.jsbmb.2016.04.008)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chen WS, Feng EL, Aggarwal R, Foye A, Beer TM, Alumkal JJ, Gleave M, Chi KN, Reiter RE & Rettig MB, et al.2020 Germline polymorphisms associated with impaired survival outcomes and somatic tumor alterations in advanced prostate cancer. Prostate Cancer and Prostatic Diseases 23 316–323. (https://doi.org/10.1038/s41391-019-0188-4)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cui D, Li J, Zhu Z, Berk M, Hardaway A, McManus J, Chung YM, Alyamani M, Valle S & Tiwari R, et al.2023 Cancer-associated fibroblast-secreted glucosamine alters the androgen biosynthesis program in prostate cancer via HSD3B1 upregulation. Journal of Clinical Investigation 133 e161913. (https://doi.org/10.1172/JCI161913)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cunningham JM, Hebbring SJ, McDonnell SK, Cicek MS, Christensen GB, Wang L, Jacobsen SJ, Cerhan JR, Blute ML & Schaid DJ, et al.2007 Evaluation of genetic variations in the androgen and estrogen metabolic pathways as risk factors for sporadic and familial prostate cancer. Cancer Epidemiology, Biomarkers and Prevention 16 969–978. (https://doi.org/10.1158/1055-9965.EPI-06-0767)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ganguly S, Lone Z, Muskara A, Imamura J, Hardaway A, Patel M, Berk M, Smile TD, Davicioni E & Stephans KL, et al.2023 Intratumoral androgen biosynthesis associated with 3β-hydroxysteroid dehydrogenase 1 promotes resistance to radiotherapy in prostate cancer. Journal of Clinical Investigation 133 e165718. (https://doi.org/10.1172/JCI165718)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Geller J, Albert J, Loza D, Geller S, Stoeltzing W & & de la Vega D 1978 DHT concentrations in human prostate cancer tissue. Journal of Clinical Endocrinology and Metabolism 46 440–444. (https://doi.org/10.1210/jcem-46-3-440)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Geller J, Albert J, Nachtsheim D, Loza D & & Lippman S 1979 Steroid levels in cancer of the prostate-markers of tumor differentiation and adequacy of anti-androgen therapy. Progress in Clinical and Biological Research 33 103–111.

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Graham LS, True LD, Gulati R, Schade GR, Wright J, Grivas P, Yezefski T, Nega K, Alexander K & Hou WM, et al.2021 Targeting backdoor androgen synthesis through AKR1C3 inhibition: a presurgical hormonal ablative neoadjuvant trial in high-risk localized prostate cancer. Prostate 81 418–426. (https://doi.org/10.1002/pros.24118)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, Quist MJ, Jing X, Lonigro RJ & Brenner JC, et al.2012 The mutational landscape of lethal castration-resistant prostate cancer. Nature 487 239–243. (https://doi.org/10.1038/nature11125)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hagberg Thulin M, Nilsson ME, Thulin P, Céraline J, Ohlsson C, Damber JE & & Welén K 2016 Osteoblasts promote castration-resistant prostate cancer by altering intratumoral steroidogenesis. Molecular and Cellular Endocrinology 422 182–191. (https://doi.org/10.1016/j.mce.2015.11.013)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hahn AW, Gill DM, Nussenzveig RH, Poole A, Farnham J, Cannon-Albright L & & Agarwal N 2018 Germline variant in HSD3B1 (1245 A > C) and response to abiraterone acetate plus prednisone in men with new-onset metastatic castration-resistant prostate cancer. Clinical Genitourinary Cancer 16 288–292. (https://doi.org/10.1016/j.clgc.2018.03.006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Han FF, Ren LL, Xuan LL, Lv YL, Liu H, Gong LL, An ZL & & Liu LH 2021 HSD3B1 variant and androgen-deprivation therapy outcome in prostate cancer. Cancer Chemotherapy and Pharmacology 87 103–112. (https://doi.org/10.1007/s00280-020-04192-z)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Harper ME, Pike A, Peeling WB & & Griffiths K 1974 Steroids of adrenal origin metabolized by human prostatic tissue both in vivo and in vitro. Journal of Endocrinology 60 117–125. (https://doi.org/10.1677/joe.0.0600117)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hearn JWD, AbuAli G, Reichard CA, Reddy CA, Magi-Galluzzi C, Chang KH, Carlson R, Rangel L, Reagan K & Davis BJ, et al.2016 HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study. Lancet 17 1435–1444. (https://doi.org/10.1016/S1470-2045(1630227-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hearn JWD, Xie W, Nakabayashi M, Almassi N, Reichard CA, Pomerantz M, Kantoff PW & & Sharifi N 2018 Association of HSD3B1 genotype with response to androgen-deprivation therapy for biochemical recurrence after radiotherapy for localized prostate cancer. JAMA Oncology 4 558–562. (https://doi.org/10.1001/jamaoncol.2017.3164)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hearn JWD, Sweeney CJ, Almassi N, Reichard CA, Reddy CA, Li H, Hobbs B, Jarrard DF, Chen YH & Dreicer R, et al.2020 HSD3B1 genotype and clinical outcomes in metastatic castration-sensitive prostate cancer. JAMA Oncology 6 e196496. (https://doi.org/10.1001/jamaoncol.2019.6496)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Heinlein CA & & Chang C 2004 Androgen receptor in prostate cancer. Endocrine Reviews 25 276–308. (https://doi.org/10.1210/er.2002-0032)

  • Hettel D, Zhang A, Alyamani M, Berk M & & Sharifi N 2018 AR signaling in prostate cancer regulates a feed-forward mechanism of androgen synthesis by way of HSD3B1 upregulation. Endocrinology 159 2884–2890. (https://doi.org/10.1210/en.2018-00283)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hou Z, Huang S, Mei Z, Chen L, Guo J, Gao Y, Zhuang Q, Zhang X, Tan Q & Yang T, et al.2022 Inhibiting 3βHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer. Cell Reports 3 100561. (https://doi.org/10.1016/j.xcrm.2022.100561)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Huang J, Hagberg Thulin M, Damber JE & & Welén K 2021 The roles of RUNX2 and osteoclasts in regulating expression of steroidogenic enzymes in castration-resistant prostate cancer cells. Molecular and Cellular Endocrinology 535 111380. (https://doi.org/10.1016/j.mce.2021.111380)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Huggins C & & Hodges CV 1941 Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Research 1 293–297. (https://doi.org/10.3322/canjclin.22.4.232)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Huhtaniemi R, Oksala R, Knuuttila M, Mehmood A, Aho E, Laajala TD, Nicorici D, Aittokallio T, Laiho A & Elo L, et al.2018 Adrenals contribute to growth of castration-resistant VCaP prostate cancer xenografts. American Journal of Pathology 188 2890–2901. (https://doi.org/10.1016/j.ajpath.2018.07.029)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Imamura J, Ganguly S, Muskara A, Liao RS, Nguyen JK, Weight C, Wee CE, Gupta S & & Mian OY 2023 Lineage plasticity and treatment resistance in prostate cancer: the intersection of genetics, epigenetics, and evolution. Frontiers in Endocrinology 14 1191311. (https://doi.org/10.3389/fendo.2023.1191311)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Khalaf DJ, Aragón IM, Annala M, Lozano R, Taavitsainen S, Lorente D, Finch DL, Romero-Laorden N, Vergidis J & Cendón Y, et al.2020 HSD3B1 (1245A>C) germline variant and clinical outcomes in metastatic castration-resistant prostate cancer patients treated with abiraterone and enzalutamide: results from two prospective studies. Annals of Oncology 31 1186–1197. (https://doi.org/10.1016/j.annonc.2020.06.006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Labrie F, Cusan L, Gomez JL, Martel C, Bérubé R, Bélanger P, Bélanger A, Vandenput L, Mellström D & & Ohlsson C 2009 Comparable amounts of sex steroids are made outside the gonads in men and women: strong lesson for hormone therapy of prostate and breast cancer. Journal of Steroid Biochemistry and Molecular Biology 113 52–56. (https://doi.org/10.1016/j.jsbmb.2008.11.004)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lambert A, Frost J, Mitchell R & & Robertson WR 1986 On the assessment of the in vitro biopotency and site(s) of action of drugs affecting adrenal steroidogenesis. Annals of Clinical Biochemistry 23 225–229. (https://doi.org/10.1177/000456328602300301)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lévesque É, Huang SP, Audet-Walsh É, Lacombe L, Bao BY, Fradet Y, Laverdière I, Rouleau M, Huang CY & Yu CC, et al.2013 Molecular markers in key steroidogenic pathways, circulating steroid levels, and prostate cancer progression. Clinical Cancer Research 19 699–709. (https://doi.org/10.1158/1078-0432.CCR-12-2812)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li R, Evaul K, Sharma KK, Chang KH, Yoshimoto J, Liu J, Auchus RJ & & Sharifi N 2012 Abiraterone inhibits 3β-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in castration-resistant prostate cancer. Clinical Cancer Research 18 3571–3579. (https://doi.org/10.1158/1078-0432.CCR-12-0908)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li Z, Bishop AC, Alyamani M, Garcia JA, Dreicer R, Bunch D, Liu J, Upadhyay SK, Auchus RJ & & Sharifi N 2015 Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer. Nature 523 347–351. (https://doi.org/10.1038/nature14406)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li Z, Alyamani M, Li J, Rogacki K, Abazeed M, Upadhyay SK, Balk SP, Taplin ME, Auchus RJ & & Sharifi N 2016 Redirecting abiraterone metabolism to fine-tune prostate cancer anti-androgen therapy. Nature 533 547–551. (https://doi.org/10.1038/nature17954)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li X, Berk M, Goins C, Alyamani M, Chung YM, Wang C, Patel M, Rathi N, Zhu Z & Willard B, et al.2023 BMX controls 3βHSD1 and sex steroid biosynthesis in cancer. Journal of Clinical Investigation 133 e163498. (https://doi.org/10.1172/JCI163498)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lu C, Terbuch A, Dolling D, Yu J, Wang H, Chen Y, Fountain J, Bertan C, Sharp A & Carreira S, et al.2020 Treatment with abiraterone and enzalutamide does not overcome poor outcome from metastatic castration-resistant prostate cancer in men with the germline homozygous HSD3B1 c.1245C genotype. Annals of Oncology 31 1178–1185. (https://doi.org/10.1016/j.annonc.2020.04.473)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mei Z, Yang T, Liu Y, Gao Y, Hou Z, Zhuang Q, He D, Zhang X, Tan Q & Zhu X, et al.2022 Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment. Cell Reports 3 100608. (https://doi.org/10.1016/j.xcrm.2022.100608)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Miller WL & & Auchus RJ 2011 The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocrine Reviews 32 81–151. (https://doi.org/10.1210/er.2010-0013)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, True LD & & Nelson PS 2008 Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Research 68 4447–4454. (https://doi.org/10.1158/0008-5472.CAN-08-0249)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mostaghel EA, Nelson PS, Lange P, Lin DW, Taplin ME, Balk S, Ellis W, Kantoff P, Marck B & Tamae D, et al.2014 Targeted androgen pathway suppression in localized prostate cancer: a pilot study. Journal of Clinical Oncology 32 229–237. (https://doi.org/10.1200/JCO.2012.48.6431)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mostaghel EA, Zhang A, Hernandez S, Marck BT, Zhang X, Tamae D, Biehl HE, Tretiakova M, Bartlett J & Burns J, et al.2019 Contribution of adrenal glands to intratumor androgens and growth of castration-resistant prostate cancer. Clinical Cancer Research 25 426–439. (https://doi.org/10.1158/1078-0432.CCR-18-1431)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Neslund-Dudas C, Bock CH, Monaghan K, Nock NL, Yang JJ, Rundle A, Tang D & & Rybicki BA 2007 SRD5A2 and HSD3B2 polymorphisms are associated with prostate cancer risk and aggressiveness. Prostate 67 1654–1663. (https://doi.org/10.1002/pros.20625)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Neubauer E, Latif M, Krause J, Heumann A, Armbrust M, Luehr C, Fraune C, Hube-Magg C, Kluth M & Möller-Koop C, et al.2018 Up regulation of the steroid hormone synthesis regulator HSD3B2 is linked to early PSA recurrence in prostate cancer. Experimental and Molecular Pathology 105 50–56. (https://doi.org/10.1016/j.yexmp.2018.05.006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nguyen DP, Li J & & Tewari AK 2014 Inflammation and prostate cancer: the role of interleukin 6 (IL-6). BJU International 113 986–992. (https://doi.org/10.1111/bju.12452)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • O'Reilly D, Johnson P & & Buchanan PJ 2019 Hypoxia induced cancer stem cell enrichment promotes resistance to androgen deprivation therapy in prostate cancer. Steroids 152 108497. (https://doi.org/10.1016/j.steroids.2019.108497)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Park JY, Tanner JP, Sellers TA, Huang Y, Stevens CK, Dossett N, Shankar RA, Zachariah B, Heysek R & & Pow-Sang J 2007 Association between polymorphisms in HSD3B1 and UGT2B17 and prostate cancer risk. Urology 70 374–379. (https://doi.org/10.1016/j.urology.2007.03.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Patel R, Fleming J, Mui E, Loveridge C, Repiscak P, Blomme A, Harle V, Salji M, Ahmad I & Teo K, et al.2018 Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1. EMBO Molecular Medicine 10 e8347. (https://doi.org/10.15252/emmm.201708347)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Peacock JW, Takeuchi A, Hayashi N, Liu L, Tam KJ, Al Nakouzi N, Khazamipour N, Tombe T, Dejima T & Lee KC, et al.2018 SEMA3C drives cancer growth by transactivating multiple receptor tyrosine kinases via plexin B1. EMBO Molecular Medicine 10 219–238. (https://doi.org/10.15252/emmm.201707689)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Penning TM, Jin Y, Rizner TL & & Bauman DR 2008 Pre-receptor regulation of the androgen receptor. Molecular and Cellular Endocrinology 281 1–8. (https://doi.org/10.1016/j.mce.2007.10.008)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pfeiffer MJ, Smit FP, Sedelaar JPM & & Schalken JA 2011 Steroidogenic enzymes and stem cell markers are upregulated during androgen deprivation in prostate cancer. Molecular Medicine 17 657–664. (https://doi.org/10.2119/molmed.2010.00143)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Poutanen M, Hagberg Thulin M & & Härkönen P 2023 Targeting sex steroid biosynthesis for breast and prostate cancer therapy. Nature Reviews Cancer 23 686–709. (https://doi.org/10.1038/s41568-023-00609-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Prizment AE, McSweeney S, Pankratz N, Joshu CE, Hwang JH, Platz EA & & Ryan CJ 2021 Prostate cancer mortality associated with aggregate polymorphisms in androgen-regulating genes: the Atherosclerosis Risk in the Communities (ARIC) study. Cancers (Basel) 13 1958. (https://doi.org/10.3390/cancers13081958)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Qin L, Chung YM, Berk M, Naelitz B, Zhu Z, Klein E, Chakraborty AA & & Sharifi N 2022 Hypoxia-reoxygenation couples 3βHSD1 enzyme and cofactor upregulation to facilitate androgen biosynthesis and hormone therapy resistance in prostate cancer. Cancer Research 82 2417–2430. (https://doi.org/10.1158/0008-5472.CAN-21-4256)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Qin L, Berk M, Chung YM, Cui D, Zhu Z, Chakraborty AA & & Sharifi N 2024 Chronic hypoxia stabilizes 3βHSD1 via autophagy suppression. Cell Reports 43 113575. (https://doi.org/10.1016/j.celrep.2023.113575)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ross RW, Oh WK, Xie W, Pomerantz M, Nakabayashi M, Sartor O, Taplin ME, Regan MM, Kantoff PW & & Freedman M 2008 Inherited variation in the androgen pathway is associated with the efficacy of androgen-deprivation therapy in men with prostate cancer. Journal of Clinical Oncology 26 842–847. (https://doi.org/10.1200/JCO.2007.13.6804)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sabharwal N & & Sharifi N 2019 HSD3B1 genotypes conferring adrenal-restrictive and adrenal-permissive phenotypes in prostate cancer and beyond. Endocrinology 160 2180–2188. (https://doi.org/10.1210/en.2019-00366)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sakai M, Martinez-Arguelles DB, Aprikian AG, Magliocco AM & & Papadopoulos V 2016 De novo steroid biosynthesis in human prostate cell lines and biopsies. Prostate 76 575–587. (https://doi.org/10.1002/pros.23146)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sang J, Chu J, Zhao X, Quan H, Ji Z, Wang S, Tang Y, Hu Z, Li H & Li L, et al.2023 Curcuminoids inhibit human and rat placental 3β-hydroxysteroid dehydrogenases: structure-activity relationship and in silico docking analysis. Journal of Ethnopharmacology 305 116051. (https://doi.org/10.1016/j.jep.2022.116051)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Schmidt KT, Huitema ADR, Chau CH & & Figg WD 2021 Resistance to second-generation androgen receptor antagonists in prostate cancer. Nature Review of Urology 18 209–226. (https://doi.org/10.1038/s41585-021-00438-4)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Semaan L, Mander N, Cher ML & & Chinni SR 2019 TMPRSS2-ERG fusions confer efficacy of enzalutamide in an in vivo bone tumor growth model. BMC Cancer 19 972. (https://doi.org/10.1186/s12885-019-6185-0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Setlur SR, Chen CX, Hossain RR, Ha JS, Van Doren VE, Stenzel B, Steiner E, Oldridge D, Kitabayashi N & Banerjee S, et al.2010 Genetic variation of genes involved in dihydrotestosterone metabolism and the risk of prostate cancer. Cancer Epidemiology, Biomarkers and Prevention 19 229–239. (https://doi.org/10.1158/1055-9965.EPI-09-1018)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sharifi N & & Auchus RJ 2012 Steroid biosynthesis and prostate cancer. Steroids 77 719–726. (https://doi.org/10.1016/j.steroids.2012.03.015)

  • Shiota M & & Eto M 2016 Current status of primary pharmacotherapy and future perspectives toward upfront therapy for metastatic hormone-sensitive prostate cancer. International Journal of Urology 23 360–369. (https://doi.org/10.1111/iju.13091)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shiota M, Fujimoto N, Yokomizo A, Takeuchi A, Itsumi M, Inokuchi J, Tatsugami K, Uchiumi T & & Naito S 2015 SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy. European Journal of Cancer 51 1962–1969. (https://doi.org/10.1016/j.ejca.2015.06.122)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shiota M, Narita S, Akamatsu S, Fujimoto N, Sumiyoshi T, Fujiwara M, Uchiumi T, Habuchi T, Ogawa O & & Eto M 2019 aAssociation of missense polymorphism in HSD3B1 with outcomes among men with prostate cancer treated with androgen-deprivation therapy or abiraterone. JAMA Network Open 2 e190115. (https://doi.org/10.1001/jamanetworkopen.2019.0115)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shiota M, Fujimoto N, Kashiwagi E & & Eto M 2019 bThe role of nuclear receptors in prostate cancer. Cells 8 602. (https://doi.org/10.3390/cells8060602)

  • Shiota M, Akamatsu S, Narita S, Sumiyoshi T, Fujiwara M, Uchiumi T, Ogawa O, Habuchi T & & Eto M 2021 The association between missense polymorphisms in SRD5A2 and HSD3B1 and treatment failure with abiraterone for castration-resistant prostate cancer. Pharmacogenomics Journal 21 440–445. (https://doi.org/10.1038/s41397-021-00220-0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shiota M, Akamatsu S, Tsukahara S, Nagakawa S, Matsumoto T & & Eto M 2022 aAndrogen receptor mutations for precision medicine in prostate cancer. Endocrine-Related Cancer 29 R143–R155. (https://doi.org/10.1530/ERC-22-0140)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shiota M, Fujimoto N, Sekino Y, Tsukahara S, Nagakawa S, Takamatsu D, Abe T, Kinoshita F, Ueda S & Ushijima M, et al.2022 bClinical impact of HSD3B1 polymorphism by metastatic volume and somatic HSD3B1 alterations in advanced prostate cancer. Andrologia 54 e14307. (https://doi.org/10.1111/and.14307)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shiota M, Endo S, Blas L, Fujimoto N & & Eto M 2023 aSteroidogenesis in castration-resistant prostate cancer. Urologic Oncology 41 240–251. (https://doi.org/10.1016/j.urolonc.2022.10.018)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shiota M, Inoue R, Tashiro K, Kobayashi K, Horiyama S, Kanji H, Eto M, Egawa S, Haginaka J & & Matsuyama H 2023b A phase II trial of abiraterone with dutasteride for second-generation antiandrogen- and chemotherapy-naïve patients with castration-resistant prostate cancer. Journal of Clinical Pharmacology 63 445–454. (https://doi.org/10.1002/jcph.2191)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shiota M, Ushijima M, Tsukahara S, Nagakawa S, Blas L, Takamatsu D, Kobayashi S, Matsumoto T, Inokuchi J & & Eto M 2023 cNR5A2/HSD3B1 pathway promotes cellular resistance to second-generation antiandrogen darolutamide. Drug Resistance Updates 70 100990. (https://doi.org/10.1016/j.drup.2023.100990)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, Febbo PG & & Balk SP 2006 Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Research 66 2815–2825. (https://doi.org/10.1158/0008-5472.CAN-05-4000)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Takahashi Y, Narita S, Shiota M, Miura M, Kagaya H, Kashima S, Yamamoto R, Nara T, Huang M & Numakura K, et al.2023 Impact of trough abiraterone level on adverse events in patients with prostate cancer treated with abiraterone acetate. European Journal of Clinical Pharmacology 79 89–98. (https://doi.org/10.1007/s00228-022-03420-0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Takizawa I, Nishiyama T, Hara N, Hoshii T, Ishizaki F, Miyashiro Y & & Takahashi K 2010 Trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, has an agonistic activity on androgen receptor in human prostate cancer cells. Cancer Letters 297 226–230. (https://doi.org/10.1016/j.canlet.2010.05.015)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Taplin ME, Montgomery B, Logothetis CJ, Bubley GJ, Richie JP, Dalkin BL, Sanda MG, Davis JW, Loda M & True LD, et al.2014 Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate in patients with localized high-risk prostate cancer: results of a randomized phase II neoadjuvant study. Journal of Clinical Oncology 32 3705–3715. (https://doi.org/10.1200/JCO.2013.53.4578)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, Arora VK, Kaushik P, Cerami E & Reva B, et al.2010 Integrative genomic profiling of human prostate cancer. Cancer Cell 18 11–22. (https://doi.org/10.1016/j.ccr.2010.05.026)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Terzic J, Abu El Maaty MA, Lutzing R, Vincent A, El Bizri R, Jung M, Keime C & & Metzger D 2023 Hypoxia-inducible factor 1A inhibition overcomes castration resistance of prostate tumors. EMBO Molecular Medicine 15 e17209. (https://doi.org/10.15252/emmm.202217209)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Titus MA, Schell MJ, Lih FB, Tomer KB & & Mohler JL 2005 Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clinical Cancer Research 11 4653–4657. (https://doi.org/10.1158/1078-0432.CCR-05-0525)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D & Kwon A, et al.2009 Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324 787–790. (https://doi.org/10.1126/science.1168175)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Trump DL, Havlin KH, Messing EM, Cummings KB, Lange PH & & Jordan VC 1989 High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects. Journal of Clinical Oncology 7 1093–1098. (https://doi.org/10.1200/JCO.1989.7.8.1093)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wu G, Huang S, Nastiuk KL, Li J, Gu J, Wu M, Zhang Q, Lin H & & Wu D 2015 Variant allele of HSD3B1 increases progression to castration-resistant prostate cancer. Prostate 75 777–782. (https://doi.org/10.1002/pros.22967)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yenki P, Bhasin S, Liu L, Nabavi N, Cheng CW, Tam KJ, Peacock JW, Adomat HH, Tombe T & Fazli L, et al.2023 Semaphorin 3C promotes de novo steroidogenesis in prostate cancer cells. Endocrine-Related Cancer 30 e230010. (https://doi.org/10.1530/ERC-23-0010)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yuan X, Cai C, Chen S, Chen S, Yu Z & & Balk SP 2014 Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis. Oncogene 33 2815–2825. (https://doi.org/10.1038/onc.2013.235)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang X, Wang Z, Huang S, He D, Yan W, Zhuang Q, Wang Z, Wang C, Tan Q & Liu Z, et al.2023 Active DHEA uptake in the prostate gland correlates with aggressive prostate cancer. Journal of Clinical Investigation 133 e171199. (https://doi.org/10.1172/JCI171199)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhuang Q, Huang S & & Li Z 2023 Prospective role of 3βHSD1 in prostate cancer precision medicine. Prostate 83 619–627. (https://doi.org/10.1002/pros.24504)

  • Zurth C, Koskinen M, Fricke R, Prien O, Korjamo T, Graudenz K, Denner K, Bairlein M, von Bühler CJ & Wilkinson G, et al.2019 Drug-drug interaction potential of darolutamide: in vitro and clinical studies. European Journal of Drug Metabolism and Pharmacokinetics 44 747–759. (https://doi.org/10.1007/s13318-019-00577-5)

    • PubMed
    • Search Google Scholar
    • Export Citation