The Journal of Urology
Volume 179, Issue 4 , Pages 1235-1242 , April 2008

The Rationale for Inhibiting 5α-Reductase Isoenzymes in the Prevention and Treatment of Prostate Cancer

  • Donald J. Tindall

      Affiliations

    • Corresponding Author InformationCorrespondence: Department of Urology Research, Mayo Clinic, 200 1st St. Southwest, Rochester, Minnesota 55905 (telephone: 507-284-8553; FAX: 507-284-2384).
  • ,
  • Roger S. Rittmaster

Received 9 May 2007

References 

  1. Zhou ZX, Lane MV, Kemppainen JA, French FS, Wilson EM. Specificity of ligand-dependent androgen receptor stabilization: receptor domain interactions influence ligand dissociation and receptor stability. Mol Endocrinol. 1995;9:208
  2. Wright AS, Thomas LN, Douglas RC, Lazier CB, Rittmaster RS. Relative potency of testosterone and dihydrotestosterone in preventing atrophy and apoptosis in the prostate of the castrated rat. J Clin Invest. 1996;98:2558
  3. Dehm SM, Tindall DJ. Molecular regulation of androgen action in prostate cancer. J Cell Biochem. 2006;99:333
  4. Kurita T, Wang YZ, Donjacour AA, Zhao C, Lydon JP, O’Malley BW, et al. Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system. Cell Death Differ. 2001;8:192
  5. Joseph IB, Nelson JB, Denmeade SR, Isaacs JT. Androgens regulate vascular endothelial growth factor content in normal and malignant prostatic tissue. Clin Cancer Res. 1997;3:2507
  6. Nelson WG, De Marzo AM, DeWeese TL, Isaacs WB. The role of inflammation in the pathogenesis of prostate cancer. J Urol. 2004;172:S6;part 2
  7. De Marzo AM, Putzi MJ, Nelson WG. New concepts in the pathology of prostatic epithelial carcinogenesis. Urology. 2001;57:103
  8. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310:644
  9. Tomlins SA, Mehra R, Rhodes DR, Smith LR, Roulston D, Helgeson BE, et al. TMPRSS2: ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res. 2006;66:3396
  10. Roy-Burman P, Tindall DJ, Robins DM, Greenberg NM, Hendrix MJ, Mohla S, et al. Androgens and prostate cancer: are the descriptors valid?. Cancer Biol Ther. 2005;4:4
  11. Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med. 2004;10:33
  12. Mohler JL, Gregory CW, Ford OH, Kim D, Weaver CM, Petrusz P, et al. The androgen axis in recurrent prostate cancer. Clin Cancer Res. 2004;10:440
  13. Li TH, Zhao H, Peng Y, Beliakoff J, Brooks JD, Sun Z. A promoting role of androgen receptor in androgen-sensitive and -insensitive prostate cancer cells. Nucleic Acids Res. 2007;13:2767
  14. Debes JD, Tindall DJ. Mechanisms of androgen-refractory prostate cancer. N Engl J Med. 2004;351:1488
  15. Imperato-McGinley J, Zhu YS. Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency. Mol Cell Endocrinol. 2002;198:51
  16. Bruchovsky N, Sadar MD, Akakura K, Goldenberg SL, Matsuoka K, Rennie PS. Characterization of 5alpha-reductase gene expression in stroma and epithelium of human prostate. J Steroid Biochem Mol Biol. 1996;59:397
  17. Pelletier G, Luu-The V, Huang XF, Lapointe H, Labrie F. Localization by in situ hybridization of steroid 5alpha-reductase isozyme gene expression in the human prostate and preputial skin. J Urol. 1998;160:577
  18. Iehle C, Radvanyi F, Gil Diez de Medina S, Ouafik LH, Gerard H, Chopin D, et al. Differences in steroid 5alpha-reductase iso-enzymes expression between normal and pathological human prostate tissue. J Steroid Biochem Mol Biol. 1999;68:189
  19. 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
  20. Thomas LN, Douglas RC, Vessey JP, Gupta R, Fontaine D, Norman RW, et al. 5alpha-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium. J Urol. 2003;170:2019
  21. Thomas LN, Lazier CB, Gupta R, Norman RW, Troyer DA, O’Brien SP, et al. Differential alterations in 5alpha-reductase type 1 and type 2 levels during development and progression of prostate cancer. Prostate. 2005;63:231
  22. Titus MA, Gregory CW, Ford OH, Schell MJ, Maygarden SJ, Mohler JL. Steroid 5alpha-reductase isozymes I and II in recurrent prostate cancer. Clin Cancer Res. 2005;11:4365
  23. Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006;66:2815
  24. Xu Y, Dalrymple SL, Becker RE, Denmeade SR, Isaacs JT. Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers. Clin Cancer Res. 2006;12:4072
  25. Frye SV. Discovery and clinical development of dutasteride, a potent dual 5alpha-reductase inhibitor. Curr Top Med Chem. 2006;6:405
  26. 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 5 alpha-reductase inhibitor. J Clin Endocrinol Metab. 2004;89:2179
  27. Roehrborn CG, Andriole G, Schalken JA, Wilson T, Clark RV. Dutasteride, a novel dual 5alpha-reductase inhibitor, reduces serum DHT to a greater extent than finasteride and achieves finasteride maximal reduction in a larger proportion of patients. In: Presented at XVIIIth Congress of European Association of Urology. Madrid, Spain, March 12–15. 2003;
  28. Wright AS, Douglas RC, Thomas LN, Lazier CB, Rittmaster RS. Androgen-induced regrowth in the castrated rat ventral prostate: role of 5alpha-reductase. Endocrinology. 1999;140:4509
  29. Gleave M, Qian J, Andreou C, Pommerville P, Chin J, Casey R, et al. The effects of the dual 5alpha-reductase inhibitor dutasteride on localized prostate cancer—results from a 4-month pre-radical prostatectomy study. Prostate. 2006;66:1674
  30. Andriole GL, Humphrey P, Ray P, Gleave ME, Trachtenberg J, Thomas LN, et al. Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer. J Urol. 2004;172:915
  31. Schmidt LJ, Murillo H, Tindall DJ. Gene expression in prostate cancer cells treated with the dual 5 alpha-reductase inhibitor dutasteride. J Androl. 2004;25:944
  32. Rittmaster RS, Norman RW, Thomas LN, Rowden G. Evidence for atrophy and apoptosis in the prostates of men given finasteride. J Clin Endocrinol Metab. 1996;81:814
  33. Bologna M, Muzi P, Biordi L, Festuccia C, Vicentini C. Finasteride dose-dependently reduces the proliferation rate of the LNCaP human prostatic cancer cell line in vitro. Urology. 1995;45:282
  34. Lazier CB, Thomas LN, Douglas RC, Vessey JP, Rittmaster RS. Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line. Prostate. 2004;58:130
  35. Iczkowski KA, Qiu J, Qian J, Somerville MC, Rittmaster RS, Andriole GL, et al. The dual 5-alpha-reductase inhibitor dutasteride induces atrophic changes and decreases relative cancer volume in human prostate. Urology. 2005;65:76
  36. Civantos F, Watson RB, Pinto JE, Korman RB, Soloway MS. Finasteride effect on prostatic hyperplasia and prostate cancer: a comparative clinicopathologic study of radical prostatectomies. J Urol Pathol. 1997;6:1
  37. Andriole GL, Guess HA, Epstein JI, Wise H, Kadmon D, Crawford ED, et al. Treatment with finasteride preserves usefulness of prostate-specific antigen in the detection of prostate cancer: results of a randomized, double-blind, placebo-controlled clinical trial (PLESS Study Group. Proscar Long-term Efficacy and Safety Study). Urology. 1998;52:195
  38. Yang XJ, Lecksell K, Short K, Gottesman J, Peterson L, Bannow J, et al. Does long-term finasteride therapy affect the histologic features of benign prostatic tissue and prostate cancer on needle biopsy? (PLESS Study Group. Proscar Long-Term Efficacy and Safety Study). Urology. 1999;53:696
  39. Andriole G, Bautista M, Crawford D, Kusec J, McConnell JD, Lucia S, et al. Prostate cancer (CAP) detection in the Medical Therapy of Prostatic Symptoms (MTOPS) trial. J Urol. 2003;169(suppl.):120;abstract 466
  40. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349:215
  41. Thompson IM, Chi C, Ankerst DP, Goodman PJ, Tangen CM, Lippman SM, et al. Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. J Natl Cancer Inst. 2006;98:1128
  42. Thomas LN, Douglas RC, Lazier CB, Gupta R, Norman RW, Murphy PR, et al. Levels of 5alpha-reductase type 1 and type 2 are increased in high grade compared to low grade prostate cancer. J Urol. 2008;179:147
  43. Andriole GL, Roehrborn C, Schulman C, Slawin KM, Somerville M, Rittmaster RS. Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia. Urology. 2004;64:537
  44. Andriole G, Bostwick D, Brawley O, Gomella L, Marberger M, Tindall D, et al. Chemoprevention of prostate cancer in men at high risk: rationale and design of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial. J Urol. 2004;172:1314
  45. Fleshner N, Gomella LG, Cookson MS, Finelli A, Evans A, Taneja S, et al. Delay in the progression of low-risk prostate cancer: rationale and design of the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial. Contemp Clin Trials. 2007;28:763
  46. Andriole G, Lieber M, Smith J, Soloway M, Schroeder F, Kadmon D, et al. Treatment with finasteride following radical prostatectomy for prostate cancer. Urology. 1995;45:491
  47. Presti JC, Fair WR, Andriole G, Sogani PC, Seidmon EJ, Ferguson D, et al. Multicenter, randomized, double-blind, placebo controlled study to investigate the effect of finasteride (MK-906) on stage D prostate cancer. J Urol. 1992;148:1201
  48. Merrick GS, Butler WM, Wallner KE, Galbreath RW, Allen ZA, Kurko B. Efficacy of neoadjuvant bicalutamide and dutasteride as a cytoreductive regimen before prostate brachytherapy. Urology. 2006;68:116
  49. Singh P, Uzgare A, Litvinov I, Denmeade SR, Isaacs JT. Combinatorial androgen receptor targeted therapy for prostate cancer. Endocr Relat Cancer. 2006;13:653
  50. Tindall DJ, Dehm SM. Regulation of androgen receptor signaling in prostate cancer. Expert Rev Anticancer Ther. 2005;5:63

PII: S0022-5347(07)03074-1

doi: 10.1016/j.juro.2007.11.033

The Journal of Urology
Volume 179, Issue 4 , Pages 1235-1242 , April 2008