Outsmarting androgen receptor: Creative approaches for targeting aberrant androgen signaling in advanced prostate cancer

Expert Review of Endocrinology and Metabolism

Volumn 6, Issue 3, 2011, Pages 483-493

  Knudsen, Karen E ^a   Kelly, William Kevin ^b  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

abiraterone; androgen receptor; cell cycle; hormone therapy; prostatic adenocarcinoma; retinoblastoma

Indexed keywords

4 [3 [4 CYANO 3 (TRIFLUOROMETHYL)PHENYL] 5,5 DIMETHYL 4 OXO 2 THIOXO 1 IMIDAZOLIDINYL] 2 FLUORO N METHYLBENZAMIDE; ABIRATERONE; ABIRATERONE ACETATE; ANASTROZOLE; ANDROGEN RECEPTOR; ANTINEOPLASTIC AGENT; BICALUTAMIDE; CABAZITAXEL; CANCER VACCINE; CURCUMIN; CYPROTERONE ACETATE; DASATINIB; DEXAMETHASONE; DOCETAXEL; FLUTAMIDE; FULVESTRANT; GONADORELIN AGONIST; GONADORELIN ANTAGONIST; KETOCONAZOLE; NILUTAMIDE; ORTERONEL; PREDNISONE; SIPULCEL T; TOK 001; UNCLASSIFIED DRUG;

ADD ON THERAPY; ADRENAL INSUFFICIENCY; ADVANCED CANCER; ALTERNATIVE RNA SPLICING; ANDROGEN SYNTHESIS; BREAST CANCER; CANCER GROWTH; CANCER INCIDENCE; FLUID RETENTION; HEART DISEASE; HUMAN; HYPOKALEMIA; LIVER DYSFUNCTION; LIVER FUNCTION; MEDICAL LITERATURE; MUTATION; NAUSEA; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN PROCESSING; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; TREATMENT FAILURE; VOMITING;

EID: 79956103537     PISSN: 17446651     EISSN: 17448417     Source Type: Journal    
DOI: 10.1586/eem.11.33     Document Type: Review

References (109)

1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J. Clin. 59, 225-249 (2009).
2. Singh J, Trabulsi EJ, Gomella LG. Is there an optimal management for localized prostate cancer? Clin. Interv. Aging 5, 187-197 (2010).
3. Grubb RL, Kibel AS. High-risk localized prostate cancer: role of radical prostatectomy. Curr. Opin. Urol. 20, 204-210 (2010).
4. Garzotto M, Hung AY. Contemporary management of high-risk localized prostate cancer. Curr. Urol. Rep. 11, 159-164 (2010).
5. Stratton KL, Chang SS. Locally advanced prostate cancer, the role of surgical management. BJU Int. 104, 449-454 (2009).
6. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J. Clin. 60, 277-300 (2010).
7. Knudsen KE, Scher HI. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin. Cancer Res. 15, 4792-4798 (2009).
8. Scher HI, Sawyers CL. Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J. Clin. Oncol. 23, 8253-8261 (2005). (Pubitemid 46211563)
9. Chen Y, Sawyers CL, Scher HI. Targeting the androgen receptor pathway in prostate cancer. Curr. Opin. Pharmacol. 8, 440-448 (2008).
10. Mohler JL. A role for the androgenreceptor in clinically localized and advanced prostate cancer. Best Pract. Res. Clin. Endocrinol. Metab. 22, 357-372 (2008). (Pubitemid 351611955)
11. Knudsen KE, Penning TM. Partners in crime: deregulation of AR activity and androgen synthesis in prostate cancer. Trends Endocrinol. Metab. 21, 315-324 (2010).
12. Agus DB, Cordon-Cardo C, Fox W, et al. Prostate cancer cell cycle regulators: response to androgen withdrawal and development of androgen independence. J. Natl Cancer Inst. 91, 1869-1876 (1999).
13. Agoulnik IU, Weigel NL. Androgen receptor coactivators and prostate cancer. Adv. Exp. Med. Biol. 617, 245-255 (2008).
14. Culig Z, Bartsch G. Androgen axis in prostate cancer. J. Cell Biochem. 99, 373-381 (2006). (Pubitemid 44435555)
15. Claessens F, Denayer S, Van Tilborgh N, Kerkhofs S, Helsen C, Haelens A. Diverse roles of androgen receptor (AR) domains in AR-mediated signaling. Nucl. Recept. Signal. 6, e008 (2008).
16. Centenera MM, Harris JM, Tilley WD, Butler LM. The contribution of different androgen receptor domains to receptor dimerization and signaling. Mol. Endocrinol. 22, 2373-2382 (2008).
17. Dehm SM, Tindall DJ. Androgen receptor structural and functional elements: role and regulation in prostate cancer. Mol. Endocrinol. 21, 2855-2863 (2007). (Pubitemid 350223500)
18. Askew EB, Gampe RT Jr, Stanley TB, Faggart JL, Wilson EM. Modulation of androgen receptor activation function 2 by testosterone and dihydrotestosterone. J. Biol. Chem. 282, 25801-25816 (2007). (Pubitemid 47372778)
19. Wang Q, Li W, Zhang Y, et al. Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell 138, 245-256 (2009).
20. Wang Q, Li W, Liu XS, et al. A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth. Mol. Cell 27, 380-392 (2007). (Pubitemid 47126935)
21. Cleutjens KB, van Eekelen CC, van der Korput HA, Brinkmann AO, Trapman J. Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter. J. Biol. Chem. 271, 6379-6388 (1996). (Pubitemid 26095448)
22. Greene KL, Albertsen PC, Babaian RJ, et al. Prostate specific antigen best practice statement: 2009 update. J. Urol. 182, 2232-2241 (2009).
23. Lilja H, Ulmert D, Vickers AJ. Prostatespecific antigen and prostate cancer: prediction, detection and monitoring. Nat. Rev. Cancer 8, 268-278 (2008). (Pubitemid 351430866)
24. Jia L, Berman BP, Jariwala U, et al. Genomic androgen receptor-occupied regions with different functions, defined by histone acetylation, coregulators and transcriptional capacity. PLoS One 3, e3645 (2008).
25. Lupien M, Brown M. Cistromics of hormone-dependent cancer. Endocr. Relat. Cancer 16, 381-389 (2009).
26. Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310, 644-648 (2005). (Pubitemid 41528150)
27. Lin C, Yang L, Tanasa B, et al. Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer. Cell 139, 1069-1083 (2009).
28. Mani RS, Tomlins SA, Callahan K, et al. Induced chromosomal proximity and gene fusions in prostate cancer. Science 326, (2009).
29. Cai C, Wang H, Xu Y, Chen S, Balk SP. Reactivation of androgen receptorregulated TMPRSS2:ERG gene expression in castration-resistant prostate cancer. Cancer Res. 69, 6027-6032 (2009).
30. Clark JP, Cooper CS. ETS gene fusions in prostate cancer. Nat. Rev. Urol. 6, 429-439 (2009).
31. Zong Y, Xin L, Goldstein AS, Lawson DA, Teitell MA, Witte ON. ETS family transcription factors collaborate with alternative signaling pathways to induce carcinoma from adult murine prostate cells. Proc. Natl Acad. Sci. USA 106, 12465-12470 (2009).
32. Hunter J. Observations on certain parts of the animal oeconomy. In: The Complete Works of John Hunter. Palmer JF (Ed.). Haswell, Barrington & Haswell, PA, USA, (1841).
33. Huggins C. Effect of orchiectomy and irradiation on cancer of the prostate. Ann. Surg. 115, 1192-1200 (1942).
34. Huggins C. The treatment of cancer of the prostate: (The 1943 address in surgery before the Royal College of Physicians and Surgeons of Canada). Can. Med. Assoc. J. 50, 301-307 (1944).
35. Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J. Clin. 22, 232-240 (1972).
36. Klotz L. Maximal androgen blockade for advanced prostate cancer. Best Pract. Res. Clin. Endocrinol. Metab. 22, 331-340 (2008). (Pubitemid 351611950)
37. Beekman KW, Hussain M. Hormonal approaches in prostate cancer: application in the contemporary prostate cancer patient. Urol. Oncol. 26, 415-419 (2008). (Pubitemid 351885377)
38. Shang Y, Myers M, Brown M. Formation of the androgen receptor transcription complex. Mol. Cell 9, 601-610 (2002). (Pubitemid 34273790)
39. De Dosso S, Berthold DR. Docetaxel in the management of prostate cancer: current standard of care and future directions. Expert Opin. Pharmacother. 9, 1969-1979 (2008).
40. Sonpavde G, Sternberg CN. The role of docetaxel based therapy for prostate cancer in the era of targeted medicine. Int. J. Urol. 17, 228-240 (2010).
41. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363, 411-422 (2010).
42. de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376, 1147-1154 (2010).
43. Chen CD, Welsbie DS, Tran C, et al. Molecular determinants of resistance to antiandrogen therapy. Nat. Med. 10, 33-39 (2004). (Pubitemid 38524696)
44. Donovan MJ, Osman I, Khan FM, et al. Androgen receptor expression is associated with prostate cancer-specific survival in castrate patients with metastatic disease. BJU Int. 105, 462-467 (2010).
45. Mohler JL. Castration-recurrent prostate cancer is not androgen-independent. Adv. Exp. Med. Biol. 617, 223-234 (2008).
46. Ford OH 3rd, Gregory CW, Kim D, Smitherman AB, Mohler JL. Androgen receptor gene amplification and protein expression in recurrent prostate cancer. J. Urol. 170, 1817-1821 (2003). (Pubitemid 37254935)
47. Linja MJ, Visakorpi T. Alterations of androgen receptor in prostate cancer. J. Steroid Biochem. Mol. Biol. 92, 255-264 (2004). (Pubitemid 40128246)
48. Waltering KK, Helenius MA, Sahu B, et al. Increased expression of androgen receptor sensitizes prostate cancer cells to low levels of androgens. Cancer Res. 69, 8141-8149 (2009).
49. Wang LG, Johnson EM, Kinoshita Y, et al. Androgen receptor overexpression in prostate cancer linked to Pur a loss from a novel repressor complex. Cancer Res. 68, 2678-2688 (2008). (Pubitemid 351556265)
50. Li Y, Wang L, Zhang M, et al. LEF1 in androgen-independent prostate cancer: regulation of androgen receptor expression, prostate cancer growth, and invasion. Cancer Res. 69, 3332-3338 (2009).
51. Sharma A, Yeow WS, Ertel A, et al. The retinoblastoma tumor suppressor controls androgen signaling and human prostate cancer progression. J. Clin. Invest. 120, 4478-4492 (2010).
52. Macleod KF. The RB tumor suppressor: a gatekeeper to hormone independence in prostate cancer? J. Clin. Invest. 120, 4179-4182 (2010).
53. Mostaghel EA, Montgomery B, Nelson PS. Castration-resistant prostate cancer: targeting androgen metabolic pathways in recurrent disease. Urol. Oncol. 27, 251-257 (2009).
54. Yuan X, Balk SP. Mechanisms mediating androgen receptor reactivation after castration. Urol. Oncol. 27, 36-41 (2009).
55. Bauman DR, Steckelbroeck S, Williams MV, Peehl DM, Penning TM. Identification of the major oxidative 3a-hydroxysteroid dehydrogenase in human prostate that converts 5a-androstane-3a,17b-diol to 5a-dihydrotestosterone: a potential therapeutic target for androgen-dependent disease. Mol. Endocrinol. 20, 444-458 (2006). (Pubitemid 43152517)
56. Penning TM, Steckelbroeck S, Bauman DR, et al. Aldo-keto reductase (AKR) 1C3: role in prostate disease and the development of specific inhibitors. Mol. Cell Endocrinol. 248, 182-191 (2006).
57. Locke JA, Guns ES, Lubik AA, et al. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res. 68, 6407-6415 (2008).
58. Montgomery RB, Mostaghel EA, Vessella R, et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res. 68, 4447-4454 (2008).
59. Stanbrough M, Bubley GJ, Ross K, et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 66, 2815-2825 (2006).
60. Mostaghel EA, Page ST, Lin DW, et al. Intraprostatic androgens and androgenregulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 67, 5033-5041 (2007). (Pubitemid 46910214)
61. Geller J, Albert J, Vik A. Advantages of total androgen blockade in the treatment of advanced prostate cancer. Semin. Oncol. 15, 53-61 (1988).
62. Dillard PR, Lin MF, Khan SA. Androgenindependent prostate cancer cells acquire the complete steroidogenic potential of synthesizing testosterone from cholesterol. Mol. Cell Endocrinol. 295, 115-120 (2008).
63. Suzuki K, Nishiyama T, Hara N, Yamana K, Takahashi K, Labrie F. Importance of the intracrine metabolism of adrenal androgens in androgen-dependent prostate cancer. Prostate Cancer Prostatic Dis. 10, 301-306 (2007). (Pubitemid 47351410)
64. Ryan CJ, Smith MR, Fong L, et al. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J. Clin. Oncol. 28, 1481-1488 (2010).
65. Reid AH, Attard G, Danila DC, et al. Significant and sustained antitumor activity in post-docetaxel, castrationresistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J. Clin. Oncol. 28, 1489-1495 (2010).
66. Steinkamp MP, O'Mahony OA, Brogley M, et al. Treatment-dependent androgen receptor mutations in prostate cancer exploit multiple mechanisms to evade therapy. Cancer Res. 69, 4434-4442 (2009).
67. Brooke GN, Bevan CL. The role of androgen receptor mutations in prostate cancer progression. Curr. Genomics 10, 18-25 (2009).
68. Terada N, Shimizu Y, Yoshida T, et al. Antiandrogen withdrawal syndrome and alternative antiandrogen therapy associated with the W741C mutant androgen receptor in a novel prostate cancer xenograft. Prostate 70, 252-261 (2010).
69. Jiang Y, Palma JF, Agus DB, Wang Y, Gross ME. Detection of androgen receptor mutations in circulating tumor cells in castration-resistant prostate cancer. Clin. Chem. 56, 1492-1495 (2010).
70. Watson PA, Chen YF, Balbas MD, et al. Constitutively active androgen receptor splice variants expressed in castrationresistant prostate cancer require full-length androgen receptor. Proc. Natl Acad. Sci. USA 107, 16759-16765 (2010).
71. Sun S, Sprenger CC, Vessella RL, et al. Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. J. Clin. Invest. 120, 2715-2730 (2010).
72. Guo Z, Yang X, Sun F, et al. A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Res. 69, 2305-2313 (2009).
73. Dehm SM, Schmidt LJ, Heemers HV, Vessella RL, Tindall DJ. Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res. 68, 5469-5477 (2008).
74. Hu R, Dunn TA, Wei S, et al. Ligandindependent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res. 69, 16-22 (2009).
75. Ward RD, Weigel NL. Steroid receptor phosphorylation: assigning function to site-specific phosphorylation. Biofactors 35, 528-536 (2009).
76. Guo Z, Dai B, Jiang T, et al. Regulation of androgen receptor activity by tyrosine phosphorylation. Cancer Cell 10, 309-319 (2006). (Pubitemid 44512189)
77. Mahajan NP, Liu Y, Majumder S, et al. Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation. Proc. Natl Acad. Sci. USA 104, 8438-8443 (2007). (Pubitemid 47175506)
78. Popov VM, Wang C, Shirley LA, et al. The functional significance of nuclear receptor acetylation. Steroids 72, 221-230 (2007). (Pubitemid 46273505)
79. Dirac AM, Bernards R. The deubiquitinating enzyme USP26 is a regulator of androgen receptor signaling. Mol. Cancer Res. 8, 844-854 (2010).
80. Xu K, Shimelis H, Linn DE, et al. Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination. Cancer Cell 15, 270-282 (2009).
81. Kaikkonen S, Jaaskelainen T, Karvonen U, et al. SUMO-specific protease 1 (SENP1) reverses the hormone-augmented SUMOylation of androgen receptor and modulates gene responses in prostate cancer cells. Mol. Endocrinol. 23, 292-307 (2009).
82. Araujo J, Logothetis C. Dasatinib: a potent SRC inhibitor in clinical development for the treatment of solid tumors. Cancer Treat. Rev. 36, 492-500 (2010).
83. Saad F, Lipton A. SRC kinase inhibition: targeting bone metastases and tumor growth in prostate and breast cancer. Cancer Treat. Rev. 36, 177-184 (2010).
84. Liu Y, Karaca M, Zhang Z, Gioeli D, Earp HS, Whang YE. Dasatinib inhibits site-specific tyrosine phosphorylation of androgen receptor by Ack1 and Src kinases. Oncogene 29, 3208-3216 (2010).
85. Cai H, Babic I, Wei X, Huang J, Witte ON. Invasive prostate carcinoma driven by c-src and androgen receptor synergy. Cancer Res. 71(3), 862-872 (2011).
86. Burd CJ, Morey LM, Knudsen KE. Androgen receptor corepressors and prostate cancer. Endocr. Relat. Cancer 13, 979-994 (2006). (Pubitemid 46212560)
87. Attard G, Reid AH, de Bono JS. Abiraterone acetate is well tolerated without concomitant use of corticosteroids. J. Clin. Oncol. 28, e560-e561, author reply e562 (2010).
88. Ryan CJ, Halabi S, Ou SS, Vogelzang NJ, Kantoff P, Small EJ. Adrenal androgen levels as predictors of outcome in prostate cancer patients treated with ketoconazole plus antiandrogen withdrawal: results from a Cancer and Leukemia Group B study. Clin. Cancer Res. 13, 2030-2037 (2007). (Pubitemid 46649869)
89. Taplin ME, Regan MM, Ko YJ, et al. Phase II study of androgen synthesis inhibition with ketoconazole, hydrocortisone, and dutasteride in asymptomatic castration-resistant prostate cancer. Clin. Cancer Res. 15, 7099-7105 (2009).
90. Ryan CJ, Smith MR, Fong L, et al. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J. Clin. Oncol. 28, 1481-1488 (2010).
91. Attard G, Reid AH, Yap TA, et al. 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. 26, 4563-4571 (2008).
92. Attard G, Reid AHM, Yap TA, et al. 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, 4563-4571 (2010).
93. De Bono JS, Attard G, Reid AH, et al. Anti-tumor activity of abiraterone acetate (AA), a CYP17 inhibitor of androgen synthesis, in chemotherapy naive and docetaxel pre-treated castration resistant prostate cancer (CRPC). J. Clin. Oncol. 26 (2008) (Abstract 5005).
94. Attard G, Reid AHM, A'Hern R, et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J. Clin. Oncol. 27, 3742-3748 (2009).
95. de Bono JS, Logothetis CJ, Fizazi K, et al. Abiraterone acetate plus low dose prednisone improves overall survival in patients with metastatic castrationresistant prostate cancer who have progressed after docetaxel-based chemotherapy: results of COU-AA-301, a randomized double blinded placebo controlled Phase III study. Ann. Oncol. 21, viii3 (2010).
96. Vasaitis TS, Bruno RD, Njar VCO. CYP17 inhibitors for prostate cancer therapy. J. Steroid Biochem. Mol. Biol. DOI: 10.1016/j.jsbmb.2010.11.005 (2011) (Epub ahead of print).
97. Tran C, Ouk S, Clegg NJ, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324, 787-790 (2009).
98. Scher HI, Beer TM, Higano CS, et al. Antitumor activity of MDV3100 in a Phase I/II study of castration-resistant prostate cancer (CRPC). J. Clin. Oncol. 27 (2009) (Abstract 5011).
99. Foster WR, Car BD, Shi H, et al. Drug safety is a barrier to the discovery and development of new androgen receptor antagonists. Prostate 71(5), 480-488 (2010).
100. Narayanan R, Yepuru M, Szafran AT, et al. Discovery and mechanistic characterization of a novel selective nuclear androgen receptor exporter for the treatment of prostate cancer. Cancer Res. 70, 842-851 (2010).
101. Andersen RJ, Mawji NR, Wang J, et al. Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor. Cancer Cell 17, 535-546 (2010).
102. Baumann CK, Castiglione-Gertsch M. Clinical use of selective estrogen receptor modulators and down regulators with the main focus on breast cancer. Minerva Ginecol. 61, 517-539 (2009).
103. Buzdar A, Jonat W, Howell A, et al. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two Phase III trials. Arimidex Study Group. J. Clin. Oncol. 14, 2000-2011 (1996). (Pubitemid 26230100)
104. Vasaitis T, Belosay A, Schayowitz A, et al. Androgen receptor inactivation contributes to antitumor efficacy of 17a hydroxylase/17,20-lyase inhibitor 3b-hydroxy-17-(1H-benzimidazole-1-yl) androsta-5,16-diene in prostate cancer. Mol. Cancer Ther. 7, 2348-2357 (2008).
105. Teiten MH, Gaascht F, Eifes S, Dicato M, Diederich M. Chemopreventive potential of curcumin in prostate cancer. Genes Nutr. 5, 61-74 (2010).
106. Dorai T, Gehani N, Katz A. Therapeutic potential of curcumin in human prostate cancer-I. Curcumin induces apoptosis in both androgen-dependent and androgenindependent prostate cancer cells. Prostate Cancer Prostatic Dis. 3, 84-93 (2000). (Pubitemid 30665213)
107. Sharma RA, Euden SA, Platton SL, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin. Cancer Res. 10, 6847-6854 (2004). (Pubitemid 39383033)
108. Nakamura K, Yasunaga Y, Segawa T, et al. Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. Int. J. Oncol. 21, 825-830 (2002).
109. Clinicaltrials.gov. 2009. Search results for abiraterone http://clinicaltrials.gov/ct2/results?term=abiraterone