Hormonal therapy for prostate cancer: Toward further unraveling of androgen receptor function

Anti-Cancer Agents in Medicinal Chemistry

Volumn 9, Issue 10, 2009, Pages 1046-1051

  Sharifi, Nima ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Androgen deprivation; Androgen receptor; Antagonists; Castration resistance; CYP17; Hormonal therapy; Prostate cancer

Indexed keywords

2 HYDROXYFLUTAMIDE; ABIRATERONE ACETATE; ANDROGEN RECEPTOR; ANTINEOPLASTIC AGENT; BICALUTAMIDE; CYPROTERONE ACETATE; DIARYLTHIOHYDANTOIN DERIVATIVE; DOCETAXEL; FK 506 BINDING PROTEIN; FLUTAMIDE; KETOCONAZOLE; MDV 3100; MEGESTROL ACETATE; NILUTAMIDE; PLACEBO; PRASTERONE; PYRVINIUM EMBONATE; SELECTIVE ANDROGEN RECEPTOR MODULATOR; TESTOSTERONE; TOLUIDIDE DERIVATIVE; UNCLASSIFIED DRUG; ANTIANDROGEN; ANTINEOPLASTIC HORMONE AGONISTS AND ANTAGONISTS;

ADVANCED CANCER; ANDROGEN DEPRIVATION THERAPY; ANDROGEN SYNTHESIS; ANTINEOPLASTIC ACTIVITY; CANCER HORMONE THERAPY; CASTRATION; CLINICAL TRIAL; DARK ADAPTATION; DEHYDROGENATION; DIMERIZATION; DOWN REGULATION; DRUG ABSORPTION; DRUG ACTIVITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; GENE AMPLIFICATION; GENE CONTROL; GENE MUTATION; GENE OVEREXPRESSION; GYNECOMASTIA; HUMAN; LOW DRUG DOSE; NONHUMAN; PROSTATE CANCER; REVIEW; SIDE EFFECT; TESTOSTERONE BLOOD LEVEL; TREATMENT RESPONSE; UPREGULATION; ANIMAL; MALE; METABOLISM; PHYSIOLOGY; PROSTATIC NEOPLASMS;

ANDROGEN ANTAGONISTS; ANIMALS; ANTINEOPLASTIC AGENTS, HORMONAL; HUMANS; MALE; PROSTATIC NEOPLASMS; RECEPTORS, ANDROGEN;

EID: 73349111609     PISSN: 18715206     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152009789735044     Document Type: Review

References (82)

1. Gottlieb, B.; Beitel, L. K.; Wu, J. H.; Trifiro, M. The androgen receptor gene mutations database (ARDB): 2004 update. Hum. Mutat., 2004, 23 (6), 527-33.
2. Tomlins, S. A.; Mehra, R.; Rhodes, D. R.; Cao, X.; Wang, L.; Dhanasekaran, S. M.; Kalyana-Sundaram, S.; Wei, J. T.; Rubin, M. A.; Pienta, K. J.; Shah, R. B.; Chinnaiyan, A. M. Integrative molecular concept modeling of prostate cancer progression. Nat. Genet., 2007, 39 (1), 41-51.
3. Mangelsdorf, D. J.; Thummel, C.; Beato, M.; Herrlich, P.; Schutz, G.; Umesono, K.; Blumberg, B.; Kastner, P.; Mark, M.; Chambon, P.; Evans, R. M. The nuclear receptor superfamily: the second decade. Cell, 1995, 83 (6), 835-9.
4. Tyagi, R. K.; Lavrovsky, Y.; Ahn, S. C.; Song, C. S.; Chatterjee, B.; Roy, A. K. Dynamics of intracellular movement and nucleocytoplasmic recycling of the ligand-activated androgen receptor in living cells. Mol. Endocrinol., 2000, 14 (8), 1162-74.
5. DePrimo, S. E.; Diehn, M.; Nelson, J. B.; Reiter, R. E.; Matese, J.; Fero, M.; Tibshirani, R.; Brown, P. O.; Brooks, J. D. Transcriptional programs activated by exposure of human prostate cancer cells to androgen. Genome. Biol., 2002, 3(7), Research0032.
6. Wilson, J. D. The role of 5alpha-reduction in steroid hormone physiology. Reprod. Fertil. Dev., 2001, 13 (7-8), 673-8.
7. Wang, Q.; Li, W.; Liu, X. S.; Carroll, J. S.; Janne, O. A.; Keeton, E. K.; Chinnaiyan, A. M.; Pienta, K. J.; Brown, M. A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth. Mol. Cell, 2007, 27 (3), 380-92.
8. Jia, L.; Berman, B. P.; Jariwala, U.; Yan, X.; Cogan, J. P.; Walters, A.; Chen, T.; Buchanan, G.; Frenkel, B.; Coetzee, G. A. Genomic androgen receptor-occupied regions with different functions, defined by histone acetylation, coregulators and transcriptional capacity. PLoS ONE, 2008, 3 (11), e3645.
9. Tomlins, S. A.; Rhodes, D. R.; Perner, S.; Dhanasekaran, S. M.; Mehra, R.; Sun, X. W.; Varambally, S.; Cao, X.; Tchinda, J.; Kuefer, R.; Lee, C.; Montie, J. E.; Shah, R. B.; Pienta, K. J.; Rubin, M. A.; Chinnaiyan, A. M. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science, 2005, 310 (5748), 644-8.
10. Walsh, P. C.; DeWeese, T. L.; Eisenberger, M. A. Clinical practice. Localized prostate cancer. N. Engl. J. Med., 2007, 357 (26), 2696-705.
11. Sharifi, N.; Gulley, J. L.; Dahut, W. L. Androgen deprivation therapy for prostate cancer. JAMA, 2005, 294 (2), 238-44.
12. Tolis, G.; Ackman, D.; Stellos, A.; Mehta, A.; Labrie, F.; Fazekas, A. T.; Comaru-Schally, A. M.; Schally, A. V. Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists. Proc. Natl. Acad. Sci. USA, 1982, 79 (5), 1658-62.
13. Limonta, P.; Montagnani Marelli, M.; Moretti, R. M. LHRH analogues as anticancer agents: pituitary and extrapituitary sites of action. Expert Opin. Investig. Drugs, 2001, 10 (4), 709-20.
14. Bubley, G. J.; Carducci, M.; Dahut, W.; Dawson, N.; Daliani, D.; Eisenberger, M.; Figg, W. D.; Freidlin, B.; Halabi, S.; Hudes, G.; Hussain, M.; Kaplan, R.; Myers, C.; Oh, W.; Petrylak, D. P.; Reed, E.; Roth, B.; Sartor, O.; Scher, H.; Simons, J.; Sinibaldi, V.; Small, E. J.; Smith, M. R.; Trump, D. L.; Wilding, G. Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J. Clin. Oncol. 1999, 17 (11), 3461-7.
15. Kuhn, J. M.; Billebaud, T.; Navratil, H.; Moulonguet, A.; Fiet, J.; Grise, P.; Louis, J. F.; Costa, P.; Husson, J. M.; Dahan, R.; et al. Prevention of the transient adverse effects of a gonadotropin-releasing hormone analogue (buserelin) in metastatic prostatic carcinoma by administration of an antiandrogen (nilutamide). N. Engl. J. Med. 1989, 321 (7), 413-8.
16. Klotz, L.; Boccon-Gibod, L.; Shore, N. D.; Andreou, C.; Persson, B. E.; Cantor, P.; Jensen, J. K.; Olesen, T. K.; Schroder, F. H. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int., 2008, 102 (11), 1531-8.
17. Crawford, E. D.; Eisenberger, M. A.; McLeod, D. G.; Spaulding, J. T.; Benson, R.; Dorr, F. A.; Blumenstein, B. A.; Davis, M. A.; Goodman, P. J. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N. Engl. J. Med., 1989, 321 (7), 419-24.
18. Eisenberger, M. A.; Blumenstein, B. A.; Crawford, E. D.; Miller, G.; McLeod, D. G.; Loehrer, P. J.; Wilding, G.; Sears, K.; Culkin, D. J.; Thompson, I. M., Jr.; Bueschen, A. J.; Lowe, B. A. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N. Engl. J. Med., 1998, 339 (15), 1036-42.
19. McPhaul, M. J. Mechanisms of prostate cancer progression to androgen independence. Best Pract. Res. Clin. Endocrinol. Metab., 2008, 22 (2), 373-88.
20. Scher, H. I.; Sawyers, C. L. Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J. Clin. Oncol. 2005, 23 (32), 8253-61.
21. Mostaghel, E. A.; Montgomery, R. B.; Lin, D. W. The basic biochemistry and molecular events of hormone therapy. Curr. Urol. Rep., 2007, 8 (3), 224-32.
22. Mostaghel, E. A.; Page, S. T.; Lin, D. W.; Fazli, L.; Coleman, I. M.; True, L. D.; Knudsen, B.; Hess, D. L.; Nelson, C. C.; Matsumoto, A. M.; Bremner, W. J.; Gleave, M. E.; Nelson, P. S. Intra-prostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res., 2007, 67 (10), 5033-41.
23. Page, S. T.; Lin, D. W.; Mostaghel, E. A.; Hess, D. L.; True, L. D.; Amory, J. K.; Nelson, P. S.; Matsumoto, A. M.; Bremner, W. J. Persistent intraprostatic androgen concentrations after medical castration in healthy men. J. Clin. Endocrinol. Metab., 2006, 91 (10), 3850-6.
24. Chen, C. D.; Welsbie, D. S.; Tran, C.; Baek, S. H.; Chen, R.; Vessella, R.; Rosenfeld, M. G.; Sawyers, C. L. Molecular determinants of resistance to antiandrogen therapy. Nat. Med., 2004, 10 (1), 33-9.
25. Bubendorf, L.; Kononen, J.; Koivisto, P.; Schraml, P.; Moch, H.; Gasser, T. C.; Willi, N.; Mihatsch, M. J.; Sauter, G.; Kallioniemi, O. P. Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. Cancer Res., 1999, 59 (4), 803-6.
26. Edwards, J.; Krishna, N. S.; Grigor, K. M.; Bartlett, J. M. Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer. Br. J. Cancer, 2003, 89 (3), 552-6.
27. Leversha, M. A.; Han, J.; Asgari, Z.; Danila, D. C.; Lin, O.; Gonzalez-Espinoza, R.; Anand, A.; Lilja, H.; Heller, G.; Fleisher, M.; Scher, H. I. Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer. Clin. Cancer Res., 2009, 15 (6), 2091-7.
28. Steinkamp, M. P.; O'Mahony, O. A.; Brogley, M.; Rehman, H.; Lapensee, E. W.; Dhanasekaran, S.; Hofer, M. D.; Kuefer, R.; Chinnaiyan, A.; Rubin, M. A.; Pienta, K. J.; Robins, D. M. Treatment-dependent androgen receptor mutations in prostate cancer exploit multiple mechanisms to evade therapy. Cancer Res., 2009, 69 (10), 4434-42.
29. Veldscholte, J.; Ris-Stalpers, C.; Kuiper, G. G.; Jenster, G.; Berrevoets, C.; Claassen, E.; van Rooij, H. C.; Trapman, J.; Brinkmann, A. O.; Mulder, E. A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochem. Biophys. Res. Commun., 1990, 173 (2), 534-40.
30. Shet, M. S.; McPhaul, M.; Fisher, C. W.; Stallings, N. R.; Estabrook, R. W. Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug. Metab. Dispos., 1997, 25 (11), 1298-303.
31. Agoulnik, I. U.; Weigel, N. L. Coactivator selective regulation of androgen receptor activity. Steroids, 2009, 74 (8), 669-74.
32. Yuan, X.; Balk, S. P. Mechanisms mediating androgen receptor reactivation after castration. Urol. Oncol., 2009, 27 (1), 36-41.
33. Ponguta, L. A.; Gregory, C. W.; French, F. S.; Wilson, E. M. Site specific androgen receptor serine phosphorylation linked to epidermal growth factor dependent growth of castration-recurrent prostate cancer. J. Biol. Chem., 2008, 283(30), 20989-21001.
34. Plymate, S. R.; Haugk, K.; Coleman, I.; Woodke, L.; Vessella, R.; Nelson, P.; Montgomery, R. B.; Ludwig, D. L.; Wu, J. D. An antibody targeting the type I insulin-like growth factor receptor enhances the castration-induced response in androgen-dependent prostate cancer. Clin. Cancer Res., 2007, 13 (21), 6429-39.
35. Montgomery, R. B.; Mostaghel, E. A.; Vessella, R.; Hess, D. L.; Kalhorn, T. F.; Higano, C. S.; True, L. D.; Nelson, P. S. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res., 2008, 68 (11), 4447-54.
36. Stanbrough, M.; Bubley, G. J.; Ross, K.; Golub, T. R.; Rubin, M. A.; Penning, T. M.; Febbo, P. G.; Balk, S. P. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res., 2006, 66 (5), 2815-25.
37. Dehm, S. M.; Schmidt, L. J.; Heemers, H. V.; Vessella, R. L.; Tindall, D. J. Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res., 2008, 68 (13), 5469-77.
38. Guo, Z.; Yang, X.; Sun, F.; Jiang, R.; Linn, D. E.; Chen, H.; Kong, X.; Melamed, J.; Tepper, C. G.; Kung, H. J.; Brodie, A. M.; Edwards, J.; Qiu, Y. A novel androgen receptor splice variant is upregulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Res., 2009, 69 (6), 2305-13.
39. Hu, R.; Dunn, T. A.; Wei, S.; Isharwal, S.; Veltri, R. W.; Humphreys, E.; Han, M.; Partin, A. W.; Vessella, R. L.; Isaacs, W. B.; Bova, G. S.; Luo, J. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res., 2009, 69 (1), 16-22.
40. Gao, T.; Marcelli, M.; McPhaul, M. J. Transcriptional activation and transient expression of the human androgen receptor. J. Steroid Biochem. Mol. Biol., 1996, 59 (1), 9-20.
41. Sharifi, N.; Dahut, W. L.; Figg, W. D. Secondary hormonal therapy for prostate cancer: what lies on the horizon? BJU Int., 2008, 101 (3), 271-4.
42. Ryan, C. J.; Small, E. J. Secondary hormonal manipulations in prostate cancer. Curr. Oncol. Rep., 2005, 7 (3), 228-33.
43. Figg, W. D.; Liu, Y.; Arlen, P.; Gulley, J.; Steinberg, S. M.; Liewehr, D. J.; Cox, M. C.; Zhai, S.; Cremers, S.; Parr, A.; Yang, X.; Chen, C. C.; Jones, E.; Dahut, W. L. A randomized, phase II trial of ketoconazole plus alendronate versus ketoconazole alone in patients with androgen independent prostate cancer and bone metastases. J. Urol., 2005, 173 (3), 790-6.
44. Savidou, I.; Deutsch, M.; Soultati, A. S.; Koudouras, D.; Kafiri, G.; Dourakis, S. P. Hepatotoxicity induced by cyproterone acetate: a report of three cases. World J. Gastroenterol., 2006, 12 (46), 7551-5.
45. Taplin, M. E. Drug insight: role of the androgen receptor in the development and progression of prostate cancer. Nat. Clin. Pract. Oncol., 2007, 4 (4), 236-44.
46. Gao, W.; Bohl, C. E.; Dalton, J. T. Chemistry and structural biology of androgen receptor. Chem. Rev., 2005, 105 (9), 3352-70.
47. Goldspiel, B. R.; Kohler, D. R. Flutamide: an antiandrogen for advanced prostate cancer. DICP, 1990, 24 (6), 616-23.
48. Chan, P.; Odel, J. G. Delayed dark adaptation caused by nilutamide. J. Neuroophthalmol., 2008, 28 (2), 158-9.
49. Schellhammer, P. F.; Davis, J. W. An evaluation of bicalutamide in the treatment of prostate cancer. Clin. Prostate Cancer, 2004, 2 (4), 213-9.
50. Taplin, M. E.; Bubley, G. J.; Ko, Y. J.; Small, E. J.; Upton, M.; Rajeshkumar, B.; Balk, S. P. Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. Cancer Res., 1999, 59 (11), 2511-5.
51. Titus, M. A.; Schell, M. J.; Lih, F. B.; Tomer, K. B.; Mohler, J. L. Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin. Cancer Res., 2005, 11 (13), 4653-7.
52. Tran, C.; Ouk, S.; Clegg, N. J.; Chen, Y.; Watson, P. A.; Arora, V.; Wongvipat, J.; Smith-Jones, P. M.; Yoo, D.; Kwon, A.; Wasielewska, T.; Welsbie, D.; Chen, C. D.; Higano, C. S.; Beer, T. M.; Hung, D. T.; Scher, H. I.; Jung, M. E.; Sawyers, C. L. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science, 2009, 324 (5928), 787-90.
53. Scher, H. I., Beer, T.M., Higano, C.S., Taplin, M., Efstathiou, E., Anand, A., Hung, D., Hirmand, M., Fleisher, M. In Antitumor Activity of MDV3100 in a Phase I/II Study of Castration-Resistant Prostate Cancer (CRPC), American Society of Clinical Oncology, Orlando, Florida, Orlando, Florida, 2009.
54. Prostate Cancer Trialists' Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet, 2000, 355 (9214), 1491-8.
55. Lu, S.; Wang, A.; Dong, Z. A novel synthetic compound that interrupts androgen receptor signaling in human prostate cancer cells. Mol. Cancer Ther., 2007, 6 (7), 2057-64.
56. Jones, J. O.; Bolton, E. C.; Huang, Y.; Feau, C.; Guy, R. K.; Yamamoto, K. R.; Hann, B.; Diamond, M. I. Non-competitive androgen receptor inhibition in vitro and in vivo. Proc. Natl. Acad. Sci. USA, 2009, 106 (17), 7233-8.
57. Joseph, J. D.; Wittmann, B. M.; Dwyer, M. A.; Cui, H.; Dye, D. A.; McDonnell, D. P.; Norris, J. D. Inhibition of prostate cancer cell growth by second-site androgen receptor antagonists. Proc. Natl. Acad. Sci. USA, 2009, 106(29), 12178-12183.
58. Wang, L. H.; Yang, X. Y.; Zhang, X.; An, P.; Kim, H. J.; Huang, J.; Clarke, R.; Osborne, C. K.; Inman, J. K.; Appella, E.; Farrar, W. L. Disruption of estrogen receptor DNA-binding domain and related intramolecular communication restores tamoxifen sensitivity in resistant breast cancer. Cancer Cell, 2006, 10 (6), 487-99.
59. Wang, L. H.; Yang, X. Y.; Zhang, X.; Mihalic, K.; Fan, Y. X.; Xiao, W.; Howard, O. M.; Appella, E.; Maynard, A. T.; Farrar, W. L. Suppression of breast cancer by chemical modulation of vulnerable zinc fingers in estrogen receptor. Nat. Med., 2004, 10 (1), 40-7.
60. Lonard, D. M.; O'Malley, B. W. The expanding cosmos of nuclear receptor coactivators. Cell, 2006, 125 (3), 411-4.
61. Sharifi, N.; Hamel, E.; Lill, M. A.; Risbood, P.; Kane, C. T., Jr.; Hossain, M. T.; Jones, A.; Dalton, J. T.; Farrar, W. L. A bifunctional colchicinoid that binds to the androgen receptor. Mol. Cancer Ther., 2007, 6 (8), 2328-36.
62. Singh, P.; Hallur, G.; Anchoori, R. K.; Bakare, O.; Kageyama, Y.; Khan, S. R.; Isaacs, J. T. Rational design of novel antiandrogens for neutralizing androgen receptor function in hormone refractory prostate cancer. Prostate, 2008, 68 (14), 1570-81.
63. Auchus, R. J. Overview of dehydroepiandrosterone biosynthesis. Semin. Reprod. Med., 2004, 22 (4), 281-8.
64. Ghayee, H. K.; Auchus, R. J. Basic concepts and recent developments in human steroid hormone biosynthesis. Rev. Endocr. Metab. Disord., 2007, 8 (4), 289-300.
65. Miller, W. L.; Auchus, R. J.; Geller, D. H. The regulation of 17,20 lyase activity. Steroids, 1997, 62 (1), 133-42.
66. Gardner, D.G.; Shoback, D.; Eds. Greenspan's Basic and Clinical Endocrinology, 8th ed.; McGraw-Hill, 2007.
67. Gingras, S.; Simard, J. Induction of 3beta-hydroxysteroid dehydrogenase/isomerase type 1 expression by interleukin-4 in human normal prostate epithelial cells, immortalized keratinocytes, colon, and cervix cancer cell lines. Endocrinology, 1999, 140 (10), 4573-84.
68. Penning, T. M.; Byrns, M. C. Steroid hormone transforming aldoketo reductases and cancer. Ann. N Y. Acad. Sci., 2009, 1155, 33-42.
69. Mizrachi, D.; Auchus, R. J. Androgens, estrogens, and hydroxysteroid dehydrogenases. Mol. Cell Endocrinol., 2009, 301 (1-2), 37-42.
70. De Coster, R.; Wouters, W.; Bruynseels, J. P450-dependent enzymes as targets for prostate cancer therapy. J. Steroid Biochem. Mol. Biol., 1996, 56 (1-6 Spec No), 133-43.
71. Reid, A. H.; Attard, G.; Barrie, E.; de Bono, J. S. CYP17 inhibition as a hormonal strategy for prostate cancer. Nat. Clin. Pract. Urol., 2008, 5 (11), 610-20.
72. Santen, R. J.; Van den Bossche, H.; Symoens, J.; Brugmans, J.; DeCoster, R. Site of action of low dose ketoconazole on androgen biosynthesis in men. J. Clin. Endocrinol. Metab., 1983, 57 (4), 732-6.
73. Pont, A.; Williams, P. L.; Azhar, S.; Reitz, R. E.; Bochra, C.; Smith, E. R.; Stevens, D. A. Ketoconazole blocks testosterone synthesis. Arch. Intern. Med., 1982, 142 (12), 2137-40.
74. Small, E. J.; Halabi, S.; Dawson, N. A.; Stadler, W. M.; Rini, B. I.; Picus, J.; Gable, P.; Torti, F. M.; Kaplan, E.; Vogelzang, N. J. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J. Clin. Oncol., 2004, 22 (6), 1025-33.
75. Barrie, S. E.; Potter, G. A.; Goddard, P. M.; Haynes, B. P.; Dowsett, M.; Jarman, M. Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase). J. Steroid Biochem. Mol. Biol., 1994, 50 (5-6), 267-73.
76. Attard, G.; Reid, A. H.; Yap, T. A.; Raynaud, F.; Dowsett, M.; Settatree, S.; Barrett, M.; Parker, C.; Martins, V.; Folkerd, E.; Clark, J.; Cooper, C. S.; Kaye, S. B.; Dearnaley, D.; Lee, G.; de Bono, J. S. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J. Clin. Oncol., 2008, 26 (28), 4563-71.
77. Attard, G.; Reid, A. H.; A'Hern, R.; Parker, C.; Oommen, N. B.; Folkerd, E.; Messiou, C.; Molife, L. R.; Maier, G.; Thompson, E.; Olmos, D.; Sinha, R.; Lee, G.; Dowsett, M.; Kaye, S. B.; Dearnaley, D.; Kheoh, T.; Molina, A.; de Bono, J. S. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J. Clin. Oncol., 2009.
78. Locke, J. A.; Guns, E. S.; Lubik, A. A.; Adomat, H. H.; Hendy, S. C.; Wood, C. A.; Ettinger, S. L.; Gleave, M. E.; Nelson, C. C. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res., 2008, 68 (15), 6407-15.
79. Handratta, V. D.; Vasaitis, T. S.; Njar, V. C.; Gediya, L. K.; Kataria, R.; Chopra, P.; Newman, D., Jr.; Farquhar, R.; Guo, Z.; Qiu, Y.; Brodie, A. M. 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 (8), 2972-84.
80. Vasaitis, T.; Belosay, A.; Schayowitz, A.; Khandelwal, A.; Chopra, P.; Gediya, L. K.; Guo, Z.; Fang, H. B.; Njar, V. C.; Brodie, A. M. 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 (8), 2348-57.
81. Bruno, R. D.; Gover, T. D.; Burger, A. M.; Brodie, A. M.; Njar, V. C. 17alpha-Hydroxylase/17,20 lyase inhibitor VN/124-1 inhibits growth of androgen-independent prostate cancer cells via induction of the endoplasmic reticulum stress response. Mol. Cancer Ther., 2008, 7 (9), 2828-36.
82. Huggins, C.; Hodges, C. V. Studies on prostate cancer, I: the effect of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res., 1941, 1, 293-297.