New Hormonal Therapies for Castration-Resistant Prostate Cancer

Endocrinology and Metabolism Clinics of North America

Volumn 40, Issue 3, 2011, Pages 625-642

  Mostaghel, Elahe A ^a   Plymate, Stephen ^b  

^a Fred Hutchinson Cancer Research Center   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

Abiraterone; Androgen ablation; Castration resistant; Hormone refractory; Intracrine; Prostate cancer; Steroidogenesis

Indexed keywords

4 [3 [4 CYANO 3 (TRIFLUOROMETHYL)PHENYL] 5,5 DIMETHYL 4 OXO 2 THIOXO 1 IMIDAZOLIDINYL] 2 FLUORO N METHYLBENZAMIDE; 4 AMINO 7 TERT BUTYL 5 (4 CHLOROPHENYL)PYRAZOLO[3,4 D]PYRIMIDINE; ABIRATERONE; AKR1C3 INHIBITOR; ANDROGEN RECEPTOR; ANTIANDROGEN; ANTINEOPLASTIC AGENT; APOPTONE; BICALUTAMIDE; DASATINIB; DEXAMETHASONE; DOCETAXEL; DUTASTERIDE; EPI 001; EPOSTANE; FINASTERIDE; FLUTAMIDE; HE 3235; HEAT SHOCK PROTEIN 90 INHIBITOR; HISTONE DEACETYLASE INHIBITOR; HSD17B3 INHIBITOR; KETOCONAZOLE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; ORTERONEL; PLACEBO; PREDNISONE; SQUALENE MONOOXYGENASE; STEROID SULFATASE INHIBITOR; TESTOSTERONE; TOK 001; UNCLASSIFIED DRUG; UNINDEXED DRUG; VN 124 1;

ANDROGEN DEPRIVATION THERAPY; ANDROGEN METABOLISM; ANDROGEN SYNTHESIS; ANOREXIA; ANTINEOPLASTIC ACTIVITY; CANCER GROWTH; CASTRATION RESISTANT PROSTATE CANCER; CONSTIPATION; DOWN REGULATION; DRUG EFFICACY; DRUG POTENCY; DRUG SAFETY; EDEMA; FATIGUE; GENE AMPLIFICATION; GENE OVEREXPRESSION; GENETIC VARIABILITY; HORMONE INHIBITION; HUMAN; HYPERTENSION; HYPOKALEMIA; LEYDIG CELL; NAUSEA; NONHUMAN; PRIORITY JOURNAL; PROSTATE HYPERTROPHY; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN EXPRESSION; REVIEW; RNA SPLICING; STEROID METABOLISM; TESTOSTERONE BLOOD LEVEL; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT;

ADENOCARCINOMA; ANDROGEN ANTAGONISTS; ANIMALS; ANTINEOPLASTIC AGENTS, HORMONAL; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MALE; MODELS, BIOLOGICAL; ORCHIECTOMY; PROSTATIC NEOPLASMS; RECEPTORS, ANDROGEN; TREATMENT FAILURE;

EID: 80052248026     PISSN: 08898529     EISSN: 15584410     Source Type: Journal    
DOI: 10.1016/j.ecl.2011.05.013     Document Type: Review

References (72)

1. Chen C.D., Welsbie D.S., Tran C., et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med 2004, 10(1):33-39.
2. 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):8253-8261.
3. Holzbeierlein J., Lal P., LaTulippe E., et al. Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance. Am J Pathol 2004, 164(1):217-227.
4. Stanbrough M., Bubley G.J., Ross K., et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res 2006, 66(5):2815-2825.
5. Montgomery R.B., Mostaghel E.A., Vessella R., et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res 2008, 68(11):4447-4454.
6. Geller J., Liu J., Albert J., et al. Relationship between human prostatic epithelial cell protein synthesis and tissue dihydrotestosterone level. Clin Endocrinol (Oxf) 1987, 26(2):155-161.
7. Mohler J.L., Gregory C.W., Ford O.H., et al. The androgen axis in recurrent prostate cancer. Clin Cancer Res 2004, 10(2):440-448.
8. Nishiyama T., Hashimoto Y., Takahashi K. The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue of patients with prostate cancer. Clin Cancer Res 2004, 10(21):7121-7126.
9. Page S.T., Lin D.W., Mostaghel E.A., et al. Persistent intraprostatic androgen concentrations after medical castration in healthy men. J Clin Endocrinol Metab 2006, 91(10):3850-3856.
10. Mizokami A., Koh E., Fujita H., et al. The adrenal androgen androstenediol is present in prostate cancer tissue after androgen deprivation therapy and activates mutated androgen receptor. Cancer Res 2004, 64(2):765-771.
11. Miyamoto H., Yeh S., Lardy H., et al. Delta5-androstenediol is a natural hormone with androgenic activity in human prostate cancer cells. Proc Natl Acad Sci U S A 1998, 95(19):11083-11088.
12. Koh E., Kanaya J., Namiki M. Adrenal steroids in human prostatic cancer cell lines. Arch Androl 2001, 46(2):117-125.
13. Mizokami A., Koh E., Izumi K., et al. Prostate cancer stromal cells and LNCaP cells coordinately activate the androgen receptor through synthesis of testosterone and dihydrotestosterone from dehydroepiandrosterone. Endocr Relat Cancer 2009, 16(4):1139-1155.
14. Locke J.A., Guns E.S., Lubik A.A., et al. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res 2008, 68(15):6407-6415.
15. Auchus R.J. The backdoor pathway to dihydrotestosterone. Trends Endocrinol Metab 2004, 15(9):432-438.
16. Mostaghel E.A., Nelson P.S. Intracrine androgen metabolism in prostate cancer progression: mechanisms of castration resistance and therapeutic implications. Best Pract Res Clin Endocrinol Metab 2008, 22(2):243-258.
17. Visakorpi T., Hyytinen E., Koivisto P., et al. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet 1995, 9(4):401-406.
18. Sun S., Sprenger C.C., Vessella R.L., et al. Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. J Clin Invest 2010, 120(8):2715-2730.
19. Taplin M.E., Balk S.P. Androgen receptor: a key molecule in the progression of prostate cancer to hormone independence. J Cell Biochem 2004, 91(3):483-490.
20. Steinkamp M.P., O'Mahony O.A., Brogley M., et al. Treatment-dependent androgen receptor mutations in prostate cancer exploit multiple mechanisms to evade therapy. Cancer Res 2009, 69(10):4434-4442.
21. Veldscholte J., Berrevoets C.A., Ris-Stalpers C., et al. The androgen receptor in LNCaP cells contains a mutation in the ligand binding domain which affects steroid binding characteristics and response to antiandrogens. J Steroid Biochem Mol Biol 1992, 41(3-8):665-669.
22. Chmelar R., Buchanan G., Need E.F., et al. Androgen receptor coregulators and their involvement in the development and progression of prostate cancer. Int J Cancer 2007, 120(4):719-733.
23. Zhu P., Baek S.H., Bourk E.M., et al. Macrophage/cancer cell interactions mediate hormone resistance by a nuclear receptor derepression pathway. Cell 2006, 124(3):615-629.
24. Rahman M.M., Miyamoto H., Lardy H., et al. Inactivation of androgen receptor coregulator ARA55 inhibits androgen receptor activity and agonist effect of antiandrogens in prostate cancer cells. Proc Natl Acad Sci U S A 2003, 100(9):5124-5129.
25. Culig Z. Androgen receptor cross-talk with cell signalling pathways. Growth Factors 2004, 22(3):179-184.
26. Wu J.D., Haugk K., Woodke L., et al. Interaction of IGF signaling and the androgen receptor in prostate cancer progression. J Cell Biochem 2006, 99(2):392-401.
27. Dorff T.B., Goldman B., Pinski J.K., et al. Clinical and correlative results of SWOG S0354: a phase II trial of CNTO328 (siltuximab), a monoclonal antibody against interleukin-6, in chemotherapy-pretreated patients with castration-resistant prostate cancer. Clin Cancer Res 2010, 16(11):3028-3034.
28. Dehm S.M., Schmidt L.J., Heemers H.V., et al. Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res 2008, 68(13):5469-5477.
29. Hu R., Dunn T.A., Wei S., et al. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res 2009, 69(1):16-22.
30. 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 2009, 69(6):2305-2313.
31. Marcias G., Erdmann E., Lapouge G., et al. Identification of novel truncated androgen receptor (AR) mutants including unreported pre-mRNA splicing variants in the 22Rv1 hormone-refractory prostate cancer (PCa) cell line. Hum Mutat 2010, 31(1):74-80.
32. Watson P.A., Chen Y.F., Balbas M.D., et al. Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor. Proc Natl Acad Sci U S A 2010, 107(39):16759-16765.
33. Handratta V.D., Vasaitis T.S., Njar V.C.O., et al. 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):2972-2984.
34. O'Donnell A., Judson I., Dowsett M., et al. Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer 2004, 90(12):2317-2325.
35. Attard G., Reid A.H., 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 2009, 27(23):3742-3748.
36. Attard G., Reid A.H., Yap T.A., 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, 26(28):4563-4571.
37. Ryan C.J., Smith M.R., 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 2010, 28(9):1481-1488.
38. Ryan C.J., Halabi S., Ou S.S., et al. 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 2007, 13(7):2030-2037.
39. Reid A.H., Attard G., Danila D.C., et al. Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J Clin Oncol 2010, 28(9):1489-1495.
40. Danila D.C., Morris M.J., de Bono J.S., et al. Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. J Clin Oncol 2010, 28(9):1496-1501.
41. de Bono J.S., Logothetis C.J., Molina A., et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011, 364(21):1995-2005.
42. Dreicer R, Agus DB, MacVicar GR, et al. Safety, pharmacokinetics, and efficacy of TAK-700 in castration-resistant, metastatic prostate cancer: a phase I/II, open-label study. Paper presented at: 2010 Genitourinary Cancers Symposium. San Francisco (CA), March 7, 2010.
43. Vasaitis T., Belosay A., Schayowitz A., et al. 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):2348-2357.
44. Bruno R.D., Gover T.D., Burger A.M., et al. 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):2828-2836.
45. Taplin M.E., Regan M.M., Ko Y.J., et al. Phase II study of androgen synthesis inhibition with ketoconazole, hydrocortisone, and dutasteride in asymptomatic castration-resistant prostate cancer. Clin Cancer Res 2009, 15(22):7099-7105.
46. Bauman D., Steckelbroeck S., Peehl D., et al. Transcript profiling of the androgen signal in normal prostate, benign prostatic hyperplasia and prostate cancer. Endocrinology 2006, 147(12):5806-5816.
47. Ji Q., Chang L., Stanczyk F.Z., et al. Impaired dihydrotestosterone catabolism in human prostate cancer: critical role of AKR1C2 as a pre-receptor regulator of androgen receptor signaling. Cancer Res 2007, 67(3):1361-1369.
48. Bauman D.R., Rudnick S.I., Szewczuk L.M., et al. Development of nonsteroidal anti-inflammatory drug analogs and steroid carboxylates selective for human aldo-keto reductase isoforms: potential antineoplastic agents that work independently of cyclooxygenase isozymes. Mol Pharmacol 2005, 67(1):60-68.
49. Byrns M.C., Steckelbroeck S., Penning T.M. An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies. Biochem Pharmacol 2008, 75(2):484-493.
50. Day J.M., Tutill H.J., Purohit A., et al. Design and validation of specific inhibitors of 17beta-hydroxysteroid dehydrogenases for therapeutic application in breast and prostate cancer, and in endometriosis. Endocr Relat Cancer 2008, 15(3):665-692.
51. Evaul K., Li R., Papari-Zareei M., et al. 3beta-hydroxysteroid dehydrogenase is a possible pharmacological target in the treatment of castration-resistant prostate cancer. Endocrinology 2010, 151(8):3514-3520.
52. Thomas J.L., Bucholtz K.M., Kacsoh B. Selective inhibition of human 3beta-hydroxysteroid dehydrogenase type 1 as a potential treatment for breast cancer. J Steroid Biochem Mol Biol 2010, 125(1-2):57-65.
53. Koreckij T.D., Trauger R.J., Montgomery R.B., et al. HE3235 inhibits growth of castration-resistant prostate cancer. Neoplasia 2009, 11(11):1216-1225.
54. Ahlem C., Kennedy M., Page T., et al. 17alpha-Alkynyl 3alpha, 17beta-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism. Invest New Drugs 2010, [Epub ahead of print].
55. Montgomery RB, Morris MJ, Ryan CJ, et al. HE3235, a synthetic adrenal hormone, in patients with castration-resistant prostate cancer (CRPC): clinical phase I/II trial results. Paper presented at: 2010 Genitourinary Cancers Symposium. San Francisco (CA), March 7, 2010.
56. Liu S.V., Schally A.V., Hawes D., et al. Expression of receptors for luteinizing hormone-releasing hormone (LH-RH) in prostate cancers following therapy with LH-RH agonists. Clin Cancer Res 2010, 16(18):4675-4680.
57. Gnanapragasam V., Darby S., Khan M., et al. Evidence that prostate gonadotropin-releasing hormone receptors mediate an anti-tumourigenic response to analogue therapy in hormone refractory prostate cancer. J Pathol 2005, 206(2):205-213.
58. Pinski J., Schally A.V., Yano T., et al. Inhibition of growth of experimental prostate cancer in rats by LH-RH analogs linked to cytotoxic radicals. Prostate 1993, 23(2):165-178.
59. Emons G., Sindermann H., Engel J., et al. Luteinizing hormone-releasing hormone receptor-targeted chemotherapy using AN-152. Neuroendocrinology 2009, 90(1):15-18.
60. Pinski JK, Xiong S, Wang Q, et al. Effect of luteinizing hormone on the steroid biosynthesis pathway in prostate cancer. Paper presented at: 2010 Genitourinary Cancers Symposium. San Francisco (CA), March 7, 2010.
61. Singh P., Uzgare A., Litvinov I., et al. Combinatorial androgen receptor targeted therapy for prostate cancer. Endocr Relat Cancer 2006, 13(3):653-666.
62. Tran C., Ouk S., Clegg N.J., et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 2009, 324(5928):787-790.
63. Scher H.I., Beer T.M., Higano C.S., et al. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet 2010, 375(9724):1437-1446.
64. Leversha M.A., Han J., Asgari Z., et al. Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer. Clin Cancer Res 2009, 15(6):2091-2097.
65. Andersen R.J., Mawji N.R., 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 2010, 17(6):535-546.
66. Solit D.B., Zheng F.F., Drobnjak M., et al. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin Cancer Res 2002, 8(5):986-993.
67. Welsbie D.S., Xu J., Chen Y., et al. Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer. Cancer Res 2009, 69(3):958-966.
68. Marrocco D.L., Tilley W.D., Bianco-Miotto T., et al. Suberoylanilide hydroxamic acid (vorinostat) represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation. Mol Cancer Ther 2007, 6(1):51-60.
69. Morgan T.M., Koreckij T.D., Corey E. Targeted therapy for advanced prostate cancer: inhibition of the PI3K/Akt/mTOR pathway. Curr Cancer Drug Targets 2009, 9(2):237-249.
70. Liu Y., Karaca M., Zhang Z., et al. Dasatinib inhibits site-specific tyrosine phosphorylation of androgen receptor by Ack1 and Src kinases. Oncogene 2010, 29(22):3208-3216.
71. Koreckij T., Nguyen H., Brown L.G., et al. Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis. Br J Cancer 2009, 101(2):263-268.
72. Yu E.Y., Wilding G., Posadas E., et al. Phase II study of dasatinib in patients with metastatic castration-resistant prostate cancer. Clin Cancer Res 2009, 15(23):7421-7428.