REFERENCES
2. Nelson PS, Clegg N, Arnold H, Ferguson C, Bonham M, White J, Hood L, Lin B. The program of androgen-responsive genes in neoplastic prostate epithelium. Proc Natl Acad Sci U S A 2002;99:11890-5.
3. Saad F, Fizazi K. Androgen deprivation therapy and secondary hormone therapy in the management of hormone-sensitive and castration-resistant prostate cancer. Urology 2015;86:852-61.
4. Huggins C, Stevens RE, Hodges CV. Studies on prostatic cancer. II. The effects of castration on advanced carcinoma of the prostate gland. Arch Surg 1941;43:209.
5. James ND, Spears MR, Clarke NW, Dearnaley DP, De Bono JS, Gale J, Hetherington J, Hoskin PJ, Jones RJ, Laing R, Lester JF, McLaren D, Parker CC, Parmar MK, Ritchie AW, Russell JM, Strebel RT, Thalmann GN, Mason MD, Sydes MR. Survival with newly diagnosed metastatic prostate cancer in the "docetaxel era": data from 917 patients in the control arm of the STAMPEDE trial (MRC PR08, CRUK/06/019). Eur Urol 2015;67:1028-38.
6. Imamura Y, Sadar MD. Androgen receptor targeted therapies in castration-resistant prostate cancer: bench to clinic. Int J Urol 2016;23:654-65.
7. Seisen T, Roupret M, Gomez F, Malouf GG, Shariat SF, Peyronnet B, Spano JP, Cancel-Tassin G, Cussenot O. A comprehensive review of genomic landscape, biomarkers and treatment sequencing in castration-resistant prostate cancer. Cancer Treat Rev 2016;48:25-33.
8. Kumagai J, Hofland J, Erkens-Schulze S, Dits NF, Steenbergen J, Jenster G, Homma Y, de Jong FH, van Weerden WM. Intratumoral conversion of adrenal androgen precursors drives androgen receptor-activated cell growth in prostate cancer more potently than de novo steroidogenesis. Prostate 2013;73:1636-50.
9. Penning TM. Mechanisms of drug resistance that target the androgen axis in castration resistant prostate cancer (CRPC). J Steroid Biochem Mol Biol 2015;153:105-13.
10. Sakai M, Martinez-Arguelles DB, Aprikian AG, Magliocco AM, Papadopoulos V. De novo steroid biosynthesis in human prostate cell lines and biopsies. Prostate 2016;76:575-87.
11. Titus MA, Schell MJ, Lih FB, Tomer KB, Mohler JL. Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin Cancer Res 2005;11:4653-7.
12. Zhang W, Meng Y, Liu N, Wen XF, Yang T. Insights into chemoresistance of prostate cancer. Int J Biol Sci 2015;11:1160-70.
13. Cai C, Balk SP. Intratumoral androgen biosynthesis in prostate cancer pathogenesis and response to therapy. Endocr Relat Cancer 2011;18:R175-82.
14. Fankhauser M, Tan Y, Hong MKH, Nguyen A, Macintyre G, Haviv I, Pedersen JS, Costello AJ, Hovens CM, Corcoran NM. Canonical androstenedione reduction is the predominant source of signaling androgens in hormone-refractory prostate cancer. Clin Cancer Res 2014;20:5547-57.
15. Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, True LD, Nelson PS. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res 2008;68:4447-54.
16. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 2011;32:81-151.
17. Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, Febbo PG, Balk SP. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res 2006;66:2815-25.
18. Chang KH, Li R, Papari-Zareei M, Watumull L, Zhao YD, Auchus RJ, Sharifi N. Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer. Proc Natl Acad Sci U S A 2011;108:13728-33.
19. Campbell TJ, Tindall DJ, Figg WD. Dihydrotestosterone synthesis from adrenal precursors does not involve testosterone in castration-resistant prostate cancer. Cancer Biol Ther 2012;13:237-8.
20. Wilson JD, Auchus RJ, Leihy MW, Guryev OL, Estabrook RW, Osborn SM, Shaw G, Renfree MB. 5alpha-androstane-3alpha,17beta-diol is formed in tammar wallaby pouch young testes by a pathway involving 5alpha-pregnane-3alpha,17alpha-diol-20-one as a key intermediate. Endocrinology 2003;144:575-80.
22. Locke JA, Guns ES, Lubik AA, Adomat HH, Hendy SC, Wood CA, Ettinger SL, Gleave ME, Nelson CC. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res 2008;68:6407-15.
23. Locke JA, Nelson CC, Adomat HH, Hendy SC, Gleave ME, Guns ES. Steroidogenesis inhibitors alter but do not eliminate androgen synthesis mechanisms during progression to castration-resistance in LNCaP prostate xenografts. J Steroid Biochem Mol Biol 2009;115:126-36.
24. Stuchbery R, McCoy PJ, Hovens CM, Corcoran NM. Androgen synthesis in prostate cancer: do all roads lead to Rome? Nat Rev Urol 2017;14:49-58.
25. Missaghian E, Kempna P, Dick B, Hirsch A, Alikhani-Koupaei R, Jegou B, Mullis PE, Frey BM, Fluck CE. Role of DNA methylation in the tissue-specific expression of the CYP17A1 gene for steroidogenesis in rodents. J Endocrinol 2009;202:99-109.
26. Chung BC, Picado-Leonard J, Haniu M, Bienkowski M, Hall PF, Shively JE, Miller WL. Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues. Proc Natl Acad Sci U S A 1987;84:407-11.
27. Martinez-Arguelles DB, Papadopoulos V. Epigenetic regulation of the expression of genes involved in steroid hormone biosynthesis and action. Steroids 2010;75:467-76.
28. Fluck CE, Miller WL. GATA-4 and GATA-6 modulate tissue-specific transcription of the human gene for P450c17 by direct interaction with Sp1. Mol Endocrinol 2004;18:1144-57.
29. Yoshimoto FK, Auchus RJ. The diverse chemistry of cytochrome P450 17A1 (P450c17, CYP17A1). J Steroid Biochem Mol Biol 2015;151:52-65.
30. Estrada DF, Laurence JS, Scott EE. Substrate-modulated cytochrome P450 17A1 and cytochrome b5 interactions revealed by NMR. J Biol Chem 2013;288:17008-18.
31. Manenda MS, Hamel CJ, Masselot-Joubert L, Picard ME, Shi R. Androgen-metabolizing enzymes: a structural perspective. J Steroid Biochem Mol Biol 2016;161:54-72.
32. DeVore NM, Scott EE. Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001. Nature 2012;482:116-9.
33. Petrunak EM, DeVore NM, Porubsky PR, Scott EE. Structures of human steroidogenic cytochrome P450 17A1 with substrates. J Biol Chem 2014;289:32952-64.
34. Estrada DF, Skinner AL, Laurence JS, Scott EE. Human cytochrome P450 17A1 conformational selection: modulation by ligand and cytochrome b5. J Biol Chem 2014;289:14310-20.
35. Gomez L, Kovac JR, Lamb DJ. CYP17A1 inhibitors in castration-resistant prostate cancer. Steroids 2015;95:80-7.
36. Njar VCO, Brodie AMH. Discovery and development of galeterone (TOK-001 or VN/124-1) for the treatment of all stages of prostate cancer. J Med Chem 2015;58:2077-87.
37. Handratta VD, Vasaitis TS, Njar VC, Gediya LK, Kataria R, Chopra P, Newman D Jr, Farquhar R, Guo Z, Qiu Y, Brodie AM. Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model. J Med Chem 2005;48:2972-84.
38. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013;368:138-48.
39. Kaku T, Hitaka T, Ojida A, Matsunaga N, Adachi M, Tanaka T, Hara T, Yamaoka M, Kusaka M, Okuda T, Asahi S, Furuya S, Tasaka A. Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. Bioorg Med Chem 2011;19:6383-99.
40. Toren PJ, Kim S, Pham S, Mangalji A, Adomat H, Guns ES, Zoubeidi A, Moore W, Gleave ME. Anticancer activity of a novel selective CYP17A1 inhibitor in preclinical models of castrate-resistant prostate cancer. Mol Cancer Ther 2015;14:59-69.
41. Larsen M, Hansen CH, Rasmussen TB, Islin J, Styrishave B, Olsen L, Jorgensen FS. Structure-based optimisation of non-steroidal cytochrome P450 17A1 inhibitors. Chem Commun (Camb) 2017;53:3118-21.
42. Bonomo S, Hansen CH, Petrunak EM, Scott EE, Styrishave B, Jorgensen FS, Olsen L. Promising tools in prostate cancer research: selective non-steroidal cytochrome P450 17A1 inhibitors. Sci Rep 2016;6:29468.
43. Wang M, Fang Y, Gu S, Chen F, Zhu Z, Sun X, Zhu J. Discovery of novel 1,2,3,4-tetrahydrobenzo[4, 5]thieno[2, 3-c]pyridine derivatives as potent and selective CYP17 inhibitors. Eur J Med Chem 2017;132:157-72.
44. Penning TM, Burczynski ME, Jez JM, Lin HK, Ma H, Moore M, Ratnam K, Palackal N. Structure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3). Mol Cell Endocrinol 2001;171:137-49.
45. Sun SQ, Gu X, Gao XS, Li Y, Yu H, Xiong W, Yu H, Wang W, Li Y, Teng Y, Zhou D. Overexpression of AKR1C3 significantly enhances human prostate cancer cells resistance to radiation. Oncotarget 2016;7:48050-8.
46. Endo S, Hu D, Matsunaga T, Otsuji Y, El-Kabbani O, Kandeel M, Ikari A, Hara A, Kitade Y, Toyooka N. Synthesis of non-prenyl analogues of baccharin as selective and potent inhibitors for aldo-keto reductase 1C3. Bioorg Med Chem 2014;22:5220-33.
47. Lovering AL, Ride JP, Bunce CM, Desmond JC, Cummings SM, White SA. Crystal structures of prostaglandin D2 11-ketoreductase (AKR1C3) in complex with the nonsteroidal anti-inflammatory drugs flufenamic acid and indomethacin. Cancer Res 2004;64:1802-10.
48. Flanagan JU, Yosaatmadja Y, Teague RM, Chai MZL, Turnbull AP, Squire CJ. Crystal structures of three classes of non-steroidal anti-inflammatory drugs in complex with aldo-keto reductase 1C3. PLoS One 2012;7:e43965.
49. Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N, Ratnam K. Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones. Biochem J 2000;351:67-77.
50. Burczynski ME, Harvey RG, Penning TM. Expression and characterization of four recombinant human dihydrodiol dehydrogenase isoforms: oxidation of trans-7, 8-dihydroxy-7,8-dihydrobenzo[a]pyrene to the activated o-quinone metabolite benzo[a]pyrene-7,8-dione. Biochemistry 1998;37:6781-90.
51. Byrns MC, Jin Y, Penning TM. Inhibitors of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3): overview and structural insights. J Steroid Biochem Mol Biol 2011;125:95-104.
52. Adeniji AO, Chen M, Penning TM. AKR1C3 as a target in castrate resistant prostate cancer. J Steroid Biochem Mol Biol 2013;137:136-49.
53. Skarydova L, Hofman J, Chlebek J, Havrankova J, Kosanova K, Skarka A, Hostalkova A, Plucha T, Cahlikova L, Wsol V. Isoquinoline alkaloids as a novel type of AKR1C3 inhibitors. J Steroid Biochem Mol Biol 2014;143:250-8.
54. Tian Y, Zhao L, Wang Y, Zhang H, Xu D, Zhao X, Li Y, Li J. Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells. Asian J Androl 2016;18:607-12.
55. Akao Y, Maruyama H, Matsumoto K, Ohguchi K, Nishizawa K, Sakamoto T, Araki Y, Mishima S, Nozawa Y. Cell growth inhibitory effect of cinnamic acid derivatives from propolis on human tumor cell lines. Biol Pharm Bull 2003;26:1057-9.
56. Endo S, Matsunaga T, Kanamori A, Otsuji Y, Nagai H, Sundaram K, El-Kabbani O, Toyooka N, Ohta S, Hara A. Selective inhibition of human type-5 17beta-hydroxysteroid dehydrogenase (AKR1C3) by baccharin, a component of Brazilian propolis. J Nat Prod 2012;75:716-21.
57. Ogihara T, Tamai I, Tsuji A. Structural characterization of substrates for the anion exchange transporter in Caco-2 cells. J Pharm Sci 1999;88:1217-21.
58. Pippione AC, Dosio F, Ducime A, Federico A, Martina K, Sainas S, Frolund B, Gooyit M, Janda KD, Boschi D, Lolli ML. Substituted 4-hydroxy-1,2,3-triazoles: synthesis, characterization and first drug design applications through bioisosteric modulation and scaffold hopping approaches. Medchemcomm 2015;6:1285-92.
59. Sainas S, Pippione AC, Giorgis M, Lupino E, Goyal P, Ramondetti C, Buccinna B, Piccinini M, Braga RC, Andrade CH, Andersson M, Moritzer AC, Friemann R, Mensa S, Al-Kadaraghi S, Boschi D, Lolli ML. Design, synthesis, biological evaluation and X-ray structural studies of potent human dihydroorotate dehydrogenase inhibitors based on hydroxylated azole scaffolds. Eur J Med Chem 2017;129:287-302.
60. Pippione AC, Giraudo A, Bonanni D, Carnovale IM, Marini E, Cena C, Costale A, Zonari D, Pors K, Sadiq M, Boschi D, Oliaro-Bosso S, Lolli ML. Hydroxytriazole derivatives as potent and selective aldo-keto reductase 1C3 (AKR1C3) inhibitors discovered by bioisosteric scaffold hopping approach. Eur J Med Chem 2017;139:936-46.
61. Heinrich DM, Flanagan JU, Jamieson SM, Silva S, Rigoreau LJ, Trivier E, Raynham T, Turnbull AP, Denny WA. Synthesis and structure-activity relationships for 1-(4-(piperidin-1-ylsulfonyl)phenyl)pyrrolidin-2-ones as novel non-carboxylate inhibitors of the aldo-keto reductase enzyme AKR1C3. Eur J Med Chem 2013;62:738-44.
62. Jamieson SM, Brooke DG, Heinrich D, Atwell GJ, Silva S, Hamilton EJ, Turnbull AP, Rigoreau LJ, Trivier E, Soudy C, Samlal SS, Owen PJ, Schroeder E, Raynham T, Flanagan JU, Denny WA. 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids: highly potent and selective inhibitors of the type 5 17-beta-hydroxysteroid dehydrogenase AKR1C3. J Med Chem 2012;55:7746-58.
63. Yin YD, Fu M, Brooke DG, Heinrich DM, Denny WA, Jamieson SM. The activity of SN33638, an inhibitor of AKR1C3, on testosterone and 17beta-estradiol production and function in castration-resistant prostate cancer and ER-positive breast cancer. Front Oncol 2014;4:159.
64. Zhou W, Limonta P. AKR1C3 inhibition therapy in castration-resistant prostate cancer and breast cancer: lessons from responses to SN33638. Front Oncol 2014;4:162.
65. Flanagan JU, Atwell GJ, Heinrich DM, Brooke DG, Silva S, Rigoreau LJ, Trivier E, Turnbull AP, Raynham T, Jamieson SM, Denny WA. Morpholylureas are a new class of potent and selective inhibitors of the type 5 17-beta-hydroxysteroid dehydrogenase (AKR1C3). Bioorg Med Chem 2014;22:967-77.
66. Kikuchi A, Furutani T, Azami H, Watanabe K, Niimi T, Kamiyama Y, Kuromitsu S, Baskin-Bey E, Heeringa M, Ouatas T, Enjo K. In vitro and in vivo characterisation of ASP9521: a novel, selective, orally bioavailable inhibitor of 17beta-hydroxysteroid dehydrogenase type 5 (17betaHSD5; AKR1C3). Invest New Drugs 2014;32:860-70.
67. Yepuru M, Wu Z, Kulkarni A, Yin F, Barrett CM, Kim J, Steiner MS, Miller DD, Dalton JT, Narayanan R. Steroidogenic enzyme AKR1C3 is a novel androgen receptor-selective coactivator that promotes prostate cancer growth. Clin Cancer Res 2013;19:5613-25.
68. Loriot Y, Fizazi K, Jones RJ, Van den Brande J, Molife RL, Omlin A, James ND, Baskin-Bey E, Heeringa M, Baron B, Holtkamp GM, Ouatas T, De Bono JS. Safety, tolerability and anti-tumour activity of the androgen biosynthesis inhibitor ASP9521 in patients with metastatic castration-resistant prostate cancer: multi-centre phase I/II study. Invest New Drugs 2014;32:995-1004.
69. Enzalutamide and indomethacin in treating patients with recurrent or metastatic hormone-resistant prostate cancer. In: ClinicalTrials.gov; Identifier: NCT02935205. Available from: https://clinicaltrials.gov/ct2/show/NCT02935205. [Last accessed on 13 Nov 2017].
70. A phase II neoadjuvant study of ARN-509, abiraterone acetate, prednisone, degarelix and indomethacin in men with localized prostate cancer pre-prostatectomy. Available from: http://www.centerwatch.com/clinical-trials/listings/98162/stage-iii-prostate-adenocarcinoma-phase-ii-neoadjuvant-study/?&radius=50. [Last accessed on 13 Nov 2017].
71. Guise CP, Abbattista MR, Singleton RS, Holford SD, Connolly J, Dachs GU, Fox SB, Pollock R, Harvey J, Guilford P, Donate F, Wilson WR, Patterson AV. The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3. Cancer Res 2010;70:1573-84.
72. Manesh DM, El-Hoss J, Evans K, Richmond J, Toscan CE, Bracken LS, Hedrick A, Sutton R, Marshall GM, Wilson WR, Kurmasheva RT, Billups C, Houghton PJ, Smith MA, Carol H, Lock RB. AKR1C3 is a biomarker of sensitivity to PR-104 in preclinical models of T-cell acute lymphoblastic leukemia. Blood 2015;126:1193-202.
73. Marchais-Oberwinkler S, Henn C, Moller G, Klein T, Negri M, Oster A, Spadaro A, Werth R, Wetzel M, Xu K, Frotscher M, Hartmann RW, Adamski J. 17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) as therapeutic targets: protein structures, functions, and recent progress in inhibitor development. J Steroid Biochem Mol Biol 2011;125:66-82.
74. Poirier D. 17beta-Hydroxysteroid dehydrogenase inhibitors: a patent review. Expert Opin Ther Pat 2010;20:1123-45.
75. Day JM, Tutill HJ, Purohit A. 17ss-hydroxysteroid dehydrogenase inhibitors. Minerva Endocrinol 2010;35:87-108.
76. Olusanjo MS, Ahmed S. Inhibitors of 17-hydroxysteroid dehydrogenase type 3 (17-beta-HSD 3). Drugs Future 2009;34:555.
77. Ning X, Yang Y, Deng H, Zhang Q, Huang Y, Su Z, Fu Y, Xiang Q, Zhang S. Development of 17β-hydroxysteroid dehydrogenase type 3 as a target in hormone-dependent prostate cancer therapy. Steroids 2017;121:10-6.
78. Fink BE, Gavai AV, Tokarski JS, Goyal B, Misra R, Xiao HY, Kimball SD, Han WC, Norris D, Spires TE, You D, Gottardis MM, Lorenzi MV, Vite GD. Identification of a novel series of tetrahydrodibenzazocines as inhibitors of 17beta-hydroxysteroid dehydrogenase type 3. Bioorg Med Chem Lett 2006;16:1532-6.
79. Vicker N, Sharland CM, Heaton WB, Gonzalez AM, Bailey HV, Smith A, Springall JS, Day JM, Tutill HJ, Reed MJ, Purohit A, Potter BV. The design of novel 17beta-hydroxysteroid dehydrogenase type 3 inhibitors. Mol Cell Endocrinol 2009;301:259-65.
80. Nashev LG, Schuster D, Laggner C, Sodha S, Langer T, Wolber G, Odermatt A. The UV-filter benzophenone-1 inhibits 17beta-hydroxysteroid dehydrogenase type 3: virtual screening as a strategy to identify potential endocrine disrupting chemicals. Biochem Pharmacol 2010;79:1189-99.
81. Schuster D, Kowalik D, Kirchmair J, Laggner C, Markt P, Aebischer-Gumy C, Strohle F, Moller G, Wolber G, Wilckens T, Langer T, Odermatt A, Adamski J. Identification of chemically diverse, novel inhibitors of 17beta-hydroxysteroid dehydrogenase type 3 and 5 by pharmacophore-based virtual screening. J Steroid Biochem Mol Biol 2011;125:148-61.
82. Guzi TJ, Liu Y-T, Doll RJ, Saksena A, Girijavallabhan VM, Pachter JA. Preparation of 6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine derivatives as 17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases. Kenilworth, USA: Schering Corporation; 2004. p. 72.
83. Day JM, Foster PA, Tutill HJ, Schmidlin F, Sharland CM, Hargrave JD, Vicker N, Potter BV, Reed MJ, Purohit A. STX2171, a 17beta-hydroxysteroid dehydrogenase type 3 inhibitor, is efficacious in vivo in a novel hormone-dependent prostate cancer model. Endocr Relat Cancer 2013;20:53-64.
84. Harada K, Kubo H, Tomigahara Y, Nishioka K, Takahashi J, Momose M, Inoue S, Kojima A. Coumarins as novel 17beta-hydroxysteroid dehydrogenase type 3 inhibitors for potential treatment of prostate cancer. Bioorg Med Chem Lett 2010;20:272-5.
85. Harada K, Kubo H, Abe J, Haneta M, Conception A, Inoue S, Okada S, Nishioka K. Discovery of potent and orally bioavailable 17β-hydroxysteroid dehydrogenase type 3 inhibitors. Bioorg Med Chem 2012;20:3242-54.
86. Ohno S, Nakajima Y, Nakajin S. Triphenyltin and tributyltin inhibit pig testicular 17beta-hydroxysteroid dehydrogenase activity and suppress testicular testosterone biosynthesis. Steroids 2005;70:645-51.
87. Titus MA, Li Y, Kozyreva OG, Maher V, Godoy A, Smith GJ, Mohler JL. 5α-reductase type 3 enzyme in benign and malignant prostate. Prostate (Hoboken, NJ, U S) 2014;74:235-49.
88. Azzouni F, Godoy A, Li Y, Mohler J. The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases. Adv Urol 2012;2012:530121.
89. Li J, Ding Z, Wang Z, Lu JF, Maity SN, Navone NM, Logothetis CJ, Mills GB, Kim J. Androgen regulation of 5alpha-reductase isoenzymes in prostate cancer: implications for prostate cancer prevention. PLoS One 2011;6:e28840.
90. Gormley GJ, Stoner E, Bruskewitz RC, Imperato-McGinley J, Walsh PC, McConnell JD, Andriole GL, Geller J, Bracken BR, Tenover JS, Vaughan ED, Pappas F, Taylor A, Binkowitz B, Ng J. The effect of finasteride in men with benign prostatic hyperplasia. 1992. J Urol 2002;167:1102-8.
91. Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002;60:434-41.
92. Faller B, Farley D, Nick H. Finasteride: a slow-binding 5 alpha-reductase inhibitor. Biochemistry 1993;32:5705-10.
93. Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M. An overview on 5alpha-reductase inhibitors. Steroids 2010;75:109-53.
94. Clark RV, Hermann DJ, Cunningham GR, Wilson TH, Morrill BB, Hobbs S. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab 2004;89:2179-84.
95. Salvador JA, Pinto RM, Silvestre SM. Steroidal 5alpha-reductase and 17alpha-hydroxylase/17,20-lyase (CYP17) inhibitors useful in the treatment of prostatic diseases. J Steroid Biochem Mol Biol 2013;137:199-222.
96. Holt DA, Levy MA, Oh HJ, Erb JM, Heaslip JI, Brandt M, Lan-Hargest HY, Metcalf BW. Inhibition of steroid 5 alpha-reductase by unsaturated 3-carboxysteroids. J Med Chem 1990;33:943-50.
97. Yao Z, Xu Y, Zhang M, Jiang S, Nicklaus MC, Liao C. Discovery of a novel hybrid from finasteride and epristeride as 5α-reductase inhibitor. Bioorg Med Chem Lett 2011;21:475-8.
98. Aggarwal S, Thareja S, Bhardwaj TR, Haupenthal J, Hartmann RW, Kumar M. Synthesis and biological evaluation of novel unsaturated carboxysteroids as human 5alpha-reductase inhibitors: a legitimate approach. Eur J Med Chem 2012;54:728-39.
99. Kim S, Kim Y-U, Ma E. Synthesis and 5α-reductase inhibitory activity of C21 steroids having 1,4-diene or 4,6-diene 20-ones and 4-azasteroid 20-oximes. Molecules 2012;17:355-68.
100. Al-Mohizea AM, Al-Omar MA, Abdalla MM, Amr AG. 5alpha-reductase inhibitors, antiviral and anti-tumor activities of some steroidal cyanopyridinone derivatives. Int J Biol Macromol 2012;50:171-9.
101. Lacy JM, Kyprianou N. A tale of two trials: the impact of 5α-reductase inhibition on prostate cancer (Review). Oncol Lett 2014;8:1391-6.
102. FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer. Available from: https://www.fda.gov/Drugs/DrugSafety/ucm258314.htm. [Last accessed on 13 Nov 2017].
103. Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, Black L, Rittmaster RS. Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. Lancet 2012;379:1103-11.
104. Schroder F, Bangma C, Angulo JC, Alcaraz A, Colombel M, McNicholas T, Tammela TL, Nandy I, Castro R. Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: results from the randomised, placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS). Eur Urol 2013;63:779-87.
105. Ramalingam S, Ramamurthy VP, Njar VC. Dissecting major signaling pathways in prostate cancer development and progression: Mechanisms and novel therapeutic targets. J Steroid Biochem Mol Biol 2017;166:16-27.
106. Blessing AM, Ganesan S, Rajapakshe K, Ying Sung Y, Reddy Bollu L, Shi Y, Cheung E, Coarfa C, Chang JT, McDonnell DP, Frigo DE. Identification of a novel coregulator, SH3YL1, that interacts with the androgen receptor N-terminus. Mol Endocrinol 2015;29:1426-39.
107. Dubbink HJ, Hersmus R, Verma CS, van der Korput HA, Berrevoets CA, van Tol J, Ziel-van der Made AC, Brinkmann AO, Pike AC, Trapman J. Distinct recognition modes of FXXLF and LXXLL motifs by the androgen receptor. Mol Endocrinol 2004;18:2132-50.
108. Saporita AJ, Zhang Q, Navai N, Dincer Z, Hahn J, Cai X, Wang Z. Identification and characterization of a ligand-regulated nuclear export signal in androgen receptor. J Biol Chem 2003;278:41998-2005.
109. Shang Y, Myers M, Brown M. Formation of the androgen receptor transcription complex. Mol Cell 2002;9:601-10.
110. Lonergan PE, Tindall DJ. Androgen receptor signaling in prostate cancer development and progression. J Carcinog 2011;10:20.
111. Green SM, Mostaghel EA, Nelson PS. Androgen action and metabolism in prostate cancer. Mol Cell Endocrinol 2012;360:3-13.
112. Kahn B, Collazo J, Kyprianou N. Androgen receptor as a driver of therapeutic resistance in advanced prostate cancer. Int J Biol Sci 2014;10:588-95.
113. Shafi AA, Yen AE, Weigel NL. Androgen receptors in hormone-dependent and castration-resistant prostate cancer. Pharmacol Ther 2013;140:223-38.
114. Jarrard DF, Kinoshita H, Shi Y, Sandefur C, Hoff D, Meisner LF, Chang C, Herman JG, Isaacs WB, Nassif N. Methylation of the androgen receptor promoter CpG island is associated with loss of androgen receptor expression in prostate cancer cells. Cancer Res 1998;58:5310-4.
115. Nakayama T, Watanabe M, Suzuki H, Toyota M, Sekita N, Hirokawa Y, Mizokami A, Ito H, Yatani R, Shiraishi T. Epigenetic regulation of androgen receptor gene expression in human prostate cancers. Lab Invest 2000;80:1789-96.
116. Schulz WA, Hoffmann MJ. Epigenetic mechanisms in the biology of prostate cancer. Semin Cancer Biol 2009;19:172-80.
117. Martinez-Ariza G, Hulme C. Recent advances in allosteric androgen receptor inhibitors for the potential treatment of castration-resistant prostate cancer. Pharm Pat Anal 2015;4:387-402.
118. Lu X, Dun K, Wang Y, Yang Y, You Q, Li Z. Recent androgen receptor antagonists in prostate cancer. Mini Rev Med Chem 2014;14:655-63.
119. Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 2009;324:787-90.
120. Clegg NJ, Wongvipat J, Joseph JD, Tran C, Ouk S, Dilhas A, Chen Y, Grillot K, Bischoff ED, Cai L, Aparicio A, Dorow S, Arora V, Shao G, Qian J, Zhao H, Yang G, Cao C, Sensintaffar J, Wasielewska T, Herbert MR, Bonnefous C, Darimont B, Scher HI, Smith-Jones P, Klang M, Smith ND, De Stanchina E, Wu N, Ouerfelli O, Rix PJ, Heyman RA, Jung ME, Sawyers CL, Hager JH. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res 2012;72:1494-503.
121. Fizazi K, Albiges L, Loriot Y, Massard C. ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer. Expert Rev Anticancer Ther 2015;15:1007-17.
122. Yu Z, Cai C, Gao S, Simon NI, Shen HC, Balk SP. Galeterone prevents androgen receptor binding to chromatin and enhances degradation of mutant androgen receptor. Clin Cancer Res 2014;20:4075-85.
123. Bastos DA, Antonarakis ES. Galeterone for the treatment of advanced prostate cancer: the evidence to date. Drug Des Devel Ther 2016;10:2289-97.
124. Biron E, Bedard F. Recent progress in the development of protein-protein interaction inhibitors targeting androgen receptor-coactivator binding in prostate cancer. J Steroid Biochem Mol Biol 2016;161:36-44.
125. Ran F, Xing H, Liu Y, Zhang D, Li P, Zhao G. Recent developments in androgen receptor antagonists. Arch Pharm (Weinheim) 2015;348:757-75.
126. Tice CM, Zheng YJ. Non-canonical modulators of nuclear receptors. Bioorg Med Chem Lett 2016;26:4157-64.
127. Lallous N, Dalal K, Cherkasov A, Rennie PS. Targeting alternative sites on the androgen receptor to treat castration-resistant prostate cancer. Int J Mol Sci 2013;14:12496-519.
128. Kandil S, Westwell AD, McGuigan C. 7-Substituted umbelliferone derivatives as androgen receptor antagonists for the potential treatment of prostate and breast cancer. Bioorg Med Chem Lett 2016;26:2000-4.
129. Johnson JK, Skoda EM, Zhou J, Parrinello E, Wang D, O'Malley K, Eyer BR, Kazancioglu M, Eisermann K, Johnston PA, Nelson JB, Wang Z, Wipf P. Small molecule antagonists of the nuclear androgen receptor for the treatment of castration-resistant prostate cancer. ACS Med Chem Lett 2016;7:785-90.
130. Balog A, Rampulla R, Martin GS, Krystek SR, Attar R, Dell-John J, DiMarco JD, Fairfax D, Gougoutas J, Holst CL, Nation A, Rizzo C, Rossiter LM, Schweizer L, Shan W, Spergel S, Spires T, Cornelius G, Gottardis M, Trainor G, Vite GD, Salvati ME. Discovery of BMS-641988, a novel androgen receptor antagonist for the treatment of prostate cancer. ACS Med Chem Lett 2015;6:908-12.
131. Zhao C, Choi YH, Khadka DB, Jin Y, Lee KY, Cho WJ. Design and synthesis of novel androgen receptor antagonists via molecular modeling. Bioorg Med Chem 2016;24:789-801.
132. Yang SH, Song CH, Van HT, Park E, Khadka DB, Gong EY, Lee K, Cho WJ. SAR based design of nicotinamides as a novel class of androgen receptor antagonists for prostate cancer. J Med Chem 2013;56:3414-8.
133. Ferroni C, Pepe A, Kim YS, Lee S, Guerrini A, Parenti MD, Tesei A, Zamagni A, Cortesi M, Zaffaroni N, De Cesare M, Beretta GL, Trepel JB, Malhotra SV, Varchi G. 1,4-substituted triazoles as nonsteroidal anti-androgens for prostate cancer treatment. J Med Chem 2017;60:3082-93.
134. Buzon V, Carbo LR, Estruch SB, Fletterick RJ, Estebanez-Perpina E. A conserved surface on the ligand binding domain of nuclear receptors for allosteric control. Mol Cell Endocrinol 2012;348:394-402.
135. Estebanez-Perpina E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJ. A surface on the androgen receptor that allosterically regulates coactivator binding. Proc Natl Acad Sci U S A 2007;104:16074-9.
136. Munuganti RS, Hassona MD, Leblanc E, Frewin K, Singh K, Ma D, Ban F, Hsing M, Adomat H, Lallous N, Andre C, Jonadass JP, Zoubeidi A, Young RN, Guns ET, Rennie PS, Cherkasov A. Identification of a potent antiandrogen that targets the BF3 site of the androgen receptor and inhibits enzalutamide-resistant prostate cancer. Chem Biol 2014;21:1476-85.
137. Zhang Y, Mantravadi PK, Jobbagy S, Bao W, Koh JT. Antagonizing the androgen receptor with a biomimetic acyltransferase. ACS Chem Biol 2016;11:2797-802.
138. Myung JK, Banuelos CA, Fernandez JG, Mawji NR, Wang J, Tien AH, Yang YC, Tavakoli I, Haile S, Watt K, McEwan IJ, Plymate S, Andersen RJ, Sadar MD. An androgen receptor N-terminal domain antagonist for treating prostate cancer. J Clin Invest 2013;123:2948-60.
139. Andersen RJ, Mawji NR, Wang J, Wang G, Haile S, Myung JK, Watt K, Tam T, Yang YC, Banuelos CA, Williams DE, McEwan IJ, Wang Y, Sadar MD. Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor. Cancer Cell 2010;17:535-46.
140. Antonarakis ES, Antonarakis ES, Luo J, Chandhasin C, Osbourne E, Perabo F, Sadar MD. Targeting the N-terminal domain of the androgen receptor: a new approach for the treatment of advanced prostate cancer. Oncologist 2016;21:1427-35.
142. Shaffer PL, Jivan A, Dollins DE, Claessens F, Gewirth DT. Structural basis of androgen receptor binding to selective androgen response elements. Proc Natl Acad Sci U S A 2004;101:4758-63.
143. Diamond M, Jones J, Renslo A. Androgen receptor inhibitors, including tetrahydropyrvinium derivatives and benzoxazole compounds, and their therapeutic use. Oakland, USA: University of California; 2009:67.
144. Lim M, Otto-Duessel M, He M, Su L, Nguyen D, Chin E, Alliston T, Jones JO. Ligand-independent and tissue-selective androgen receptor inhibition by pyrvinium. ACS Chem Biol 2014;9:692-702.
145. Li H, Ban F, Dalal K, Leblanc E, Frewin K, Ma D, Adomat H, Rennie PS, Cherkasov A. Discovery of small-molecule inhibitors selectively targeting the DNA-binding domain of the human androgen receptor. J Med Chem 2014;57:6458-67.
146. Dalal K, Roshan-Moniri M, Sharma A, Li H, Ban F, Hassona MD, Hsing M, Singh K, LeBlanc E, Dehm S, Tomlinson Guns ES, Cherkasov A, Rennie PS. Selectively targeting the DNA-binding domain of the androgen receptor as a prospective therapy for prostate cancer. J Biol Chem 2014;289:26417-29.
147. Loddick SA, Ross SJ, Thomason AG, Robinson DM, Walker GE, Dunkley TP, Brave SR, Broadbent N, Stratton NC, Trueman D, Mouchet E, Shaheen FS, Jacobs VN, Cumberbatch M, Wilson J, Jones RD, Bradbury RH, Rabow A, Gaughan L, Womack C, Barry ST, Robson CN, Critchlow SE, Wedge SR, Brooks AN. AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo. Mol Cancer Ther 2013;12:1715-27.
148. Omlin A, Jones RJ, van der Noll R, Satoh T, Niwakawa M, Smith SA, Graham J, Ong M, Finkelman RD, Schellens JH, Zivi A, Crespo M, Riisnaes R, Nava-Rodrigues D, Malone MD, Dive C, Sloane R, Moore D, Alumkal JJ, Dymond A, Dickinson PA, Ranson M, Clack G, de Bono J, Elliott T. AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer - results of two parallel first-in-human phase I studies. Invest New Drugs 2015;33:679-90.
149. Yamashita S, Lai KP, Chuang KL, Xu D, Miyamoto H, Tochigi T, Pang ST, Li L, Arai Y, Kung HJ, Yeh S, Chang C. ASC-J9 suppresses castration-resistant prostate cancer growth through degradation of full-length and splice variant androgen receptors. Neoplasia 2012;14:74-83.
150. Lai KP, Huang CK, Chang YJ, Chung CY, Yamashita S, Li L, Lee SO, Yeh S, Chang C. New therapeutic approach to suppress castration-resistant prostate cancer using ASC-J9 via targeting androgen receptor in selective prostate cells. Am J Pathol 2013;182:460-73.
151. Liu C, Lou W, Zhu Y, Nadiminty N, Schwartz CT, Evans CP, Gao AC. Niclosamide inhibits androgen receptor variants expression and overcomes enzalutamide resistance in castration-resistant prostate cancer. Clin Cancer Res 2014;20:3198-210.
152. Purushottamachar P, Kwegyir-Afful AK, Martin MS, Ramamurthy VP, Ramalingam S, Njar VC. Identification of novel steroidal androgen receptor degrading agents inspired by galeterone 3β-imidazole carbamate. ACS Med Chem Lett 2016;7:708-13.
153. Kwegyir-Afful AK, Ramalingam S, Purushottamachar P, Ramamurthy VP, Njar VC. Galeterone and VNPT55 induce proteasomal degradation of AR/AR-V7, induce significant apoptosis via cytochrome c release and suppress growth of castration resistant prostate cancer xenografts in vivo. Oncotarget 2015;6:27440-60.
154. Bradbury RH, Hales NJ, Rabow AA, Walker GE, Acton DG, Andrews DM, Ballard P, Brooks NA, Colclough N, Girdwood A, Hancox UJ, Jones O, Jude D, Loddick SA, Mortlock AA. Small-molecule androgen receptor downregulators as an approach to treatment of advanced prostate cancer. Bioorg Med Chem Lett 2011;21:5442-5.
155. Gustafson JL, Neklesa TK, Cox CS, Roth AG, Buckley DL, Tae HS, Sundberg TB, Stagg DB, Hines J, McDonnell DP, Norris JD, Crews CM. Small-molecule-mediated degradation of the androgen receptor through hydrophobic tagging. Angew Chem Int Ed Engl 2015;54:9659-62.
156. Lai AC, Crews CM. Induced protein degradation: an emerging drug discovery paradigm. Nat Rev Drug Discov 2017;16:101-14.
157. Chu FM, Sartor O, Gomella L, Rudo T, Somerville MC, Hereghty B, Manyak MJ. A randomised, double-blind study comparing the addition of bicalutamide with or without dutasteride to GnRH analogue therapy in men with non-metastatic castrate-resistant prostate cancer. Eur J Cancer 2015;51:1555-69.
158. Hamid AR, Verhaegh GW, Smit FP, van Rijt-van de Westerlo C, Armandari I, Brandt A, Sweep FC, Sedelaar JP, Schalken JA. Dutasteride and enzalutamide synergistically suppress prostate tumor cell proliferation. J Urol 2015;193:1023-9.
159. Liu C, Lou W, Zhu Y, Yang JC, Nadiminty N, Gaikwad NW, Evans CP, Gao AC. Intracrine androgens and AKR1C3 activation confer resistance to enzalutamide in prostate cancer. Cancer Res 2015;75:1413-22.
160. Liu C, Armstrong CM, Lou W, Lombard A, Evans CP, Gao AC. Inhibition of AKR1C3 activation overcomes resistance to abiraterone in advanced prostate cancer. Mol Cancer Ther 2017;16:35-44.
161. Androgen receptor antagonist ARN-509, abiraterone acetate, prednisone, degarelix, and indomethacin in treating patients with localized prostate cancer before surgery. Available from: https://www.bioportfolio.com/resources/trial/162934/Androgen-Receptor-Antagonist-ARN-509-Abiraterone-Acetate-Prednisone-Degarelix-and-Indomethacin-in.html. [Last accessed on 13 Nov 2017].
162. Anighoro A, Bajorath J, Rastelli G. Polypharmacology: challenges and opportunities in drug discovery. J Med Chem 2014;57:7874-87.
163. Boschi D, Giorgis M, Cena C, Talniya NC, Di Stilo A, Morini G, Coruzzi G, Guaita E, Fruttero R, Gasco A. Multitarget drugs: synthesis and preliminary pharmacological characterization of zileuton analogues endowed with Dual 5-LO inhibitor and NO-dependent activities. Chem Med Chem 2010;5:1444-9.
164. Chen M, Adeniji AO, Twenter BM, Winkler JD, Christianson DW, Penning TM. Crystal structures of AKR1C3 containing an N-(aryl)amino-benzoate inhibitor and a bifunctional AKR1C3 inhibitor and androgen receptor antagonist. Therapeutic leads for castrate resistant prostate cancer. Bioorg Med Chem Lett 2012;22:3492-7.
165. Feau C, Arnold LA, Kosinski A, Zhu F, Connelly M, Guy RK. Novel flufenamic acid analogues as inhibitors of androgen receptor mediated transcription. ACS Chem Biol 2009;4:834-43.
166. Purushottamachar P, Godbole AM, Gediya LK, Martin MS, Vasaitis TS, Kwegyir-Afful AK, Ramalingam S, Ates-Alagoz Z, Njar VC. Systematic structure modifications of multitarget prostate cancer drug candidate galeterone to produce novel androgen receptor down-regulating agents as an approach to treatment of advanced prostate cancer. J Med Chem 2013;56:4880-98.
167. Bruno RD, Vasaitis TS, Gediya LK, Purushottamachar P, Godbole AM, Ates-Alagoz Z, Brodie AMH, Njar VC. Synthesis and biological evaluations of putative metabolically stable analogs of VN/124-1 (TOK-001): head to head anti-tumor efficacy evaluation of VN/124-1 (TOK-001) and abiraterone in LAPC-4 human prostate cancer xenograft model. Steroids 2011;76:1268-79.
168. Vasaitis T, Belosay A, Schayowitz A, Khandelwal A, Chopra P, Gediya LK, Guo Z, Fang HB, Njar VC, Brodie AM. Androgen receptor inactivation contributes to antitumor efficacy of 17{alpha}-hydroxylase/17,20-lyase inhibitor 3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene in prostate cancer. Mol Cancer Ther 2008;7:2348-57.
169. Tokai Pharmaceuticals Announces Clinical Update. Available from: http://www.businesswire.com/news/home/20160726005553/en/Tokai-Pharmaceuticals-Announces-Clinical-Update. [Last accessed on 13 Nov 2017].
170. Li Z, Bishop AC, Alyamani M, Garcia JA, Dreicer R, Bunch D, Liu J, Upadhyay SK, Auchus RJ, Sharifi N. Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer. Nature 2015;523:347-51.
171. Richards J, Lim AC, Hay CW, Taylor AE, Wingate A, Nowakowska K, Pezaro C, Carreira S, Goodall J, Arlt W, McEwan IJ, de Bono JS, Attard G. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res 2012;72:2176-82.
172. Buttigliero C, Tucci M, Bertaglia V, Vignani F, Bironzo P, Di Maio M, Scagliotti GV. Understanding and overcoming the mechanisms of primary and acquired resistance to abiraterone and enzalutamide in castration resistant prostate cancer. Cancer Treat Rev 2015;41:884-92.
173. Jernberg E, Thysell E, Bovinder YE, Rudolfsson S, Crnalic S, Widmark A, Bergh A, Wikstrom P. Characterization of prostate cancer bone metastases according to expression levels of steroidogenic enzymes and androgen receptor splice variants. PLoS One 2013;8:e77407.
174. Djusberg E, Jernberg E, Thysell E, Golovleva I, Lundberg P, Crnalic S, Widmark A, Bergh A, Brattsand M, Wikström P. High levels of the AR-V7 splice variant and co-amplification of the golgi protein coding YIPF6 in AR amplified prostate cancer bone metastases. Prostate 2017;77:625-38.
175. Hagberg Thulin M, Nilsson ME, Thulin P, Céraline J, Ohlsson C, Damber J-E, Welén K. Osteoblasts promote castration-resistant prostate cancer by altering intratumoral steroidogenesis. Mol Cell Endocrinol 2016;422:182-91.
176. Hofland J, van Weerden WM, Dits NF, Steenbergen J, van Leenders GJ, Jenster G, Schroder FH, de Jong FH. Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer. Cancer Res 2010;70:1256-64.
177. Pfeiffer MJ, Smit FP, Sedelaar JP, Schalken JA. Steroidogenic enzymes and stem cell markers are upregulated during androgen deprivation in prostate cancer. Mol Med 2011;17:657-64.
178. Audet-Walsh E, Yee T, Tam IS, Giguere V. Inverse regulation of DHT synthesis enzymes 5alpha-reductase types 1 and 2 by the androgen receptor in prostate cancer. Endocrinology 2017;158:1015-21.
179. Luo J, Dunn TA, Ewing CM, Walsh PC, Isaacs WB. Decreased gene expression of steroid 5 alpha-reductase 2 in human prostate cancer: implications for finasteride therapy of prostate carcinoma. Prostate 2003;57:134-9.
180. Thomas LN, Lazier CB, Gupta R, Norman RW, Troyer DA, O'Brien SP, Rittmaster RS. Differential alterations in 5alpha-reductase type 1 and type 2 levels during development and progression of prostate cancer. Prostate 2005;63:231-9.
181. Bjelfman C, Soderstrom TG, Brekkan E, Norlen BJ, Egevad L, Unge T, Andersson S, Rane A. Differential gene expression of steroid 5 alpha-reductase 2 in core needle biopsies from malignant and benign prostatic tissue. J Clin Endocrinol Metab 1997;82:2210-4.
182. Uemura M, Tamura K, Chung S, Honma S, Okuyama A, Nakamura Y, Nakagawa H. Novel 5 alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer. Cancer Sci 2008;99:81-6.
183. Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer 2001;1:34-45.
