Novel and next-generation androgen receptor–directed therapies for prostate cancer: Beyond abiraterone and enzalutamide

Urologic Oncology: Seminars and Original Investigations

Volumn 34, Issue 8, 2016, Pages 348-355

  Bambury, Richard M ^a   Rathkopf, Dana E ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

ARN 509; Bipolar androgen therapy; Castration resistant prostate cancer; Galeterone; ODM 201; VT 464

Indexed keywords

ABIRATERONE; ANTINEOPLASTIC HORMONE AGONISTS AND ANTAGONISTS; APALUTAMIDE; ENZALUTAMIDE; EPI 001; GALETERONE; ODM 201; SEVITERONEL; UNCLASSIFIED DRUG; 3-HYDROXY-17-(1H-BENZIMIDAZOLE-1-YL)ANDROSTA-5,16-DIENE; ANDROGEN RECEPTOR; ANDROGEN RECEPTOR ANTAGONIST; ANDROSTANE DERIVATIVE; BENZIMIDAZOLE DERIVATIVE; DAROLUTAMIDE; NAPHTHALENE DERIVATIVE; PHENYLTHIOHYDANTOIN; PYRAZOLE DERIVATIVE; THIOHYDANTOIN DERIVATIVE; TRIAZOLE DERIVATIVE; VT-464;

ANDROGEN THERAPY; ANTIANDROGEN THERAPY; BIPOLAR ANDROGEN THERAPY; CANCER HORMONE THERAPY; DRUG MECHANISM; HUMAN; MALE; MULTICENTER STUDY (TOPIC); NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROSTATE CANCER; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; ANALOGS AND DERIVATIVES; CASTRATION RESISTANT PROSTATE CANCER;

ANDROGEN RECEPTOR ANTAGONISTS; ANDROSTADIENES; ANDROSTENES; BENZIMIDAZOLES; HUMANS; MALE; NAPHTHALENES; PHENYLTHIOHYDANTOIN; PROSTATIC NEOPLASMS, CASTRATION-RESISTANT; PYRAZOLES; RECEPTORS, ANDROGEN; THIOHYDANTOINS; TRIAZOLES;

EID: 84936797820     PISSN: 10781439     EISSN: 18732496     Source Type: Journal    
DOI: 10.1016/j.urolonc.2015.05.025     Document Type: Review

References (85)

1. [1] Siegel, R., Ma, J., Zou, Z., Jemal, A., Cancer statistics, 2014. CA Cancer J Clin 64 (2014), 9–29.
2. [2] GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012; 2015. http://globocan.iarc.fr.
3. [3] Huggins, C., Stevens, R.E., Hodges, C.V., The effects of castration on advanced carcinoma of the prostate gland. Arch Surg 43 (1941), 209–223.
4. [4] Ross, R.W., Xie, W., Regan, M.M., Pomerantz, M., Nakabayashi, M., Daskivich, T.J., et al. Efficacy of androgen deprivation therapy (ADT) in patients with advanced prostate cancer: association between Gleason score, prostate-specific antigen level, and prior ADT exposure with duration of ADT effect. Cancer 112 (2008), 1247–1253.
5. [5] Scher, H.I., Heller, G., Clinical states in prostate cancer: toward a dynamic model of disease progression. Urology 55 (2000), 323–327.
6. [6] Egan, A., Dong, Y., Zhang, H., Qi, Y., Balk, S.P., Sartor, O., Castration-resistant prostate cancer: adaptive responses in the androgen axis. Cancer Treat Rev 40 (2014), 426–433.
7. [7] Wright, J.L., Kwon, E.M., Ostrander, E.A., Montgomery, R.B., Lin, D.W., Vessella, R., et al. Expression of SLCO transport genes in castration-resistant prostate cancer and impact of genetic variation in SLCO1B3 and SLCO2B1 on prostate cancer outcomes. Cancer Epidemiol Biomarkers Prev 20 (2011), 619–627.
8. [8] Yang, M., Xie, W., Mostaghel, E., Nakabayashi, M., Werner, L., Sun, T., et al. SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer. J Clin Oncol 29 (2011), 2565–2573.
9. [9] Stanbrough, M., Bubley, G.J., Ross, K., Golub, T.R., Rubin, M.A., Penning, T.M., et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res 66 (2006), 2815–2825.
10. [10] Ford, O.H. 3rd, Gregory, C.W., Kim, D., Smitherman, A.B., Mohler, J.L., Androgen receptor gene amplification and protein expression in recurrent prostate cancer. J Urol 170 (2003), 1817–1821.
11. [11] Hay, C.W., McEwan, I.J., The impact of point mutations in the human androgen receptor: classification of mutations on the basis of transcriptional activity. PLoS One, 7, 2012, e32514.
12. [12] Sun, S., Sprenger, C.C., Vessella, R.L., Haugk, K., Soriano, K., Mostaghel, E.A., et al. Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. J Clin Invest 120 (2010), 2715–2730.
13. [13] Heemers, H.V., Tindall, D.J., Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev 28 (2007), 778–808.
14. [14] Arora, V.K., Schenkein, E., Murali, R., Subudhi, S.K., Wongvipat, J., Balbas, M.D., et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell 155 (2013), 1309–1322.
15. [15] Grasso, C.S., Wu, Y.M., Robinson, D.R., Cao, X., Dhanasekaran, S.M., Khan, A.P., et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature 487 (2012), 239–243.
16. [16] Chinnaiyan AM, Sawyers CL. Precision therapy of advanced prostate cancer Stan Up To Cancer-PCF Prostate Cancer Dream Team. http://www.standup2cancer.org/progress_reports/dream_team_progress_reports_prostate_cancer.
17. [17] Scher, H.I., Fizazi, K., Saad, F., Taplin, M.E., Sternberg, C.N., Miller, K., et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367 (2012), 1187–1197.
18. [18] de Bono, J.S., Logothetis, C.J., Molina, A., Fizazi, K., North, S., Chu, L., et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364 (2011), 1995–2005.
19. [19] Beer, T.M., Armstrong, A.J., Rathkopf, D.E., Loriot, Y., Sternberg, C.N., Higano, C.S., et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371 (2014), 424–433.
20. [20] Ryan, C.J., Smith, M.R., de Bono, J.S., Molina, A., Logothetis, C.J., de Souza, P., et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368 (2013), 138–148.
21. [21] Beer TM, Armstrong AJ, Sternberg CN, Higano CS, Iversen P, Loriot Y, et al. Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): results of phase III PREVAIL study. ASCO Meeting Abstracts 2014;32(Suppl. 4):LBA1.
22. [22] Rathkopf, D., Scher, H.I., Androgen receptor antagonists in castration-resistant prostate cancer. Cancer J 19 (2013), 43–49.
23. [23] Mostaghel, E.A., Marck, B.T., Plymate, S.R., Vessella, R.L., Balk, S., Matsumoto, A.M., et al. Resistance to CYP17A1 inhibition with abiraterone in castration-resistant prostate cancer: induction of steroidogenesis and androgen receptor splice variants. Clin Cancer Res 17 (2011), 5913–5925.
24. [24] Antonarakis, E.S., Lu, C., Wang, H., Luber, B., Nakazawa, M., Roeser, J.C., et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 371 (2014), 1028–1038.
25. [25] Joseph, J.D., Lu, N., Qian, J., Sensintaffar, J., Shao, G., Brigham, D., et al. A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509. Cancer Discov 3 (2013), 1020–1029.
26. [26] Efstathiou, E., Titus, M., Wen, S., Hoang, A., Karlou, M., Ashe, R., et al. Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol 67 (2015), 53–60.
27. [27] Thomson, D., Charnley, N., Parikh, O., Enzalutamide after failure of docetaxel and abiraterone in metastatic castrate-resistant prostate cancer. Eur J Cancer 50 (2014), 1040–1041.
28. [28] Noonan, K.L., North, S., Bitting, R.L., Armstrong, A.J., Ellard, S.L., Chi, K.N., Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after enzalutamide. Ann Oncol 24 (2013), 1802–1807.
29. [29] Suzman, D.L., Luber, B., Schweizer, M.T., Nadal, R., Antonarakis, E.S., Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone. Prostate 74 (2014), 1278–1285.
30. [30] Handratta, V.D., Vasaitis, T.S., Njar, V.C., Gediya, L.K., Kataria, R., Chopra, P., 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 48 (2005), 2972–2984.
31. [31] Soifer, H.S., Souleimanian, N., Wu, S., Voskresenskiy, A.M., Collak, F.K., Cinar, B., et al. Direct regulation of androgen receptor activity by potent CYP17 inhibitors in prostate cancer cells. J Biol Chem 287 (2012), 3777–3787.
32. [32] Vasaitis, T., Belosay, A., Schayowitz, A., Khandelwal, A., Chopra, P., Gediya, L.K., 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 7 (2008), 2348–2357.
33. [33] Yu, Z., Cai, C., Gao, S., Simon, N.I., Shen, H.C., Balk, S.P., Galeterone prevents androgen receptor binding to chromatin and enhances degradation of mutant androgen receptor. Clin Cancer Res 20 (2014), 4075–4085.
34. [34] Taplin ME, Chi KN, Chu F, Cochran J, Edenfield WJ, Eisenberger M, et al. Galeterone in four castrate resistant prostate cancer populations: results from ARMOR2. ESMO Congress; 2014.
35. [35] Maity SN, Titus M, Wu G, Lu JF, Ramachandran S, Eisner JR, et al. Efficacy of VT-464, a novel selective inhibitor of cytochrome P450 17,20-lyase, in castrate-resistant prostate cancer models. AACR 2013; 2013.
36. [36] Toren, P.J., Kim, S., Pham, S., Mangalji, A., Adomat, H., Guns, E.S., et al. Anticancer activity of a novel selective CYP17A1 inhibitor in preclinical models of castrate-resistant prostate cancer. Mol Cancer Ther 14 (2015), 59–69.
37. [37] Bunim, J.J., Ziff, M., Mc, E.C., Evaluation of prolonged cortisone therapy in rheumatiod arthritis: a four-year study. Am J Med 18 (1955), 27–40.
38. [38] Huscher, D., Thiele, K., Gromnica-Ihle, E., Hein, G., Demary, W., Dreher, R., et al. Dose-related patterns of glucocorticoid-induced side effects. Ann Rheum Dis 68 (2009), 1119–1124.
39. [39] Canalis, E., Mazziotti, G., Giustina, A., Bilezikian, J.P., Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 18 (2007), 1319–1328.
40. [40] Scher H, Saad F, Chi KN, Taplin ME, Sternberg CN, Armstrong AJ, et al. Association of baseline corticosteroid with outcomes in a multivariate analysis of the Phase 3 AFFIRM study of enzalutamide (ENZA), an androgen receptor signaling inhibitor. European Society of Medical Oncology Annual Congress; 2012.
41. [41] Moore WR, Norris JD, Wardell S, Eisner JR, Hoekstra WJ, Schotzinger RJ, et al. Direct effects of the selective CYP17 lyase (L) inhibitor, VT-464, on the androgen receptor (AR) and its oral activity in an F876L tumor mouse xenograft model. ASCO Meeting Abstracts 33(Suppl. 7):263.
42. [42] De Bono JS, Pezaro CJ, GillessenS, Shore ND, Nordquist LT, Efstathiou E, et al. The oral CYP17-Lyase (L) inhibitor VT-464 in patients with CRPC. Orlando, FL: ASCO Genitourinary Cancers Symposium; 2015.
43. [43] Heesch, C.M., Neurosteroid modulation of arterial baroreflex function in the rostral ventrolateral medulla. Auton Neurosci 161 (2011), 28–33.
44. [44] Oral VT-464 in patients with castration-resistant prostate cancer previously treated with enzalutamide. https://clinicaltrials.gov/ct2/show/NCT02130700; 2014 [accessed 01.11.15].
45. [45] A study to evaluate oral VT-464 in patients with castration-resistant prostate cancer. clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02012920;2015 [accessed 01.11.15].
46. [46] Scher HI, Mostaghel EA, Taplin ME, Bambury RM. The novel CYP17 lyase inhibitor VT-464 for patients with advanced prostate cancer resistant to enzalutamide: use of predictive biomarkers during drug development process is essential for improved patient management and time to drug approval. http://www.pcf.org/site/c.leJRIROrEpH/b.9176997/k.C3F8/Challenge_Award_Recipients_2014.htm; 2014.
47. [47] Clegg, N.J., Wongvipat, J., Joseph, J.D., Tran, C., Ouk, S., Dilhas, A., et al. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res 72 (2012), 1494–1503.
48. [48] Scher, H.I., Beer, T.M., Higano, C.S., Anand, A., Taplin, M.E., Efstathiou, E., et al. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet 375 (2010), 1437–1446.
49. [49] Rathkopf, D., Liu, G., Carducci, M.A., Eisenberger, M.A., Anand, A., Morris, M.J., et al. Phase I dose-escalation study of the novel antiandrogen BMS-641988 in patients with castration-resistant prostate cancer. Clin Cancer Res 17 (2011), 880–887.
50. [50] Rathkopf, D.E., Morris, M.J., Fox, J.J., Danila, D.C., Slovin, S.F., Hager, J.H., et al. Phase I study of ARN-509, a novel antiandrogen, in the treatment of castration-resistant prostate cancer. J Clin Oncol 31 (2013), 3525–3530.
51. [51] Rathkopf DE, Antonarakis ES, Shore ND, Tutrone RF, Alumkal JJ, Ryan CJ, et al. ARN-509 in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without prior abiraterone acetate (AA) treatment. ASCO Meeting Abstracts 2014;32(Suppl. 15):5026.
52. [52] Smith MR, Antonarakis ES, Ryan CJ, et al. ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC). ASCO GU Symposium; 2013.
53. [53] clinicaltrials.gov. A study of ARN-509 in men with non-metastatic castration-resistant prostate cancer (SPARTAN). https://clinicaltrials.gov/ct2/show/NCT01946204; 2014 [accessed 01.11.15].
54. [54] clinicaltrials.gov. An efficacy and safety study of JNJ56021927 in participants with chemotherapy-naive metastatic castration-resistant prostate cancer. https://clinicaltrials.gov/ct2/show/NCT02257736; 2015.
55. [55] clinicaltrials.gov. ARN 509 plus everolimus in men with progressive metastatic castration-resistant prostate cancer after treatment with abiraterone acetate; 2014.
56. [56] Fizazi, K., Massard, C., Bono, P., Jones, R., Kataja, V., James, N., et al. Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial. Lancet Oncol 15 (2014), 975–985.
57. [57] clinicaltrials.gov. Efficacy and safety study of ODM-201 in men with high-risk non-metastatic castration-resistant prostate cancer (ARAMIS). https://clinicaltrials.gov/ct2/show/NCT02200614[accessed 01.11.15].
58. [58] Andersen, R.J., Mawji, N.R., Wang, J., Wang, G., Haile, S., Myung, J.K., 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 (2010), 535–546.
59. [59] Mostaghel, E.A., Plymate, S.R., Montgomery, B., Molecular pathways: targeting resistance in the androgen receptor for therapeutic benefit. Clin Cancer Res 20 (2014), 791–798.
60. [60] Myung, J.K., Banuelos, C.A., Fernandez, J.G., Mawji, N.R., Wang, J., Tien, A.H., et al. An androgen receptor N-terminal domain antagonist for treating prostate cancer. J Clin Invest 123 (2013), 2948–2960.
61. [61] D׳Antonio, J.M., Vander Griend, D.J., Isaacs, J.T., DNA licensing as a novel androgen receptor mediated therapeutic target for prostate cancer. Endocr Relat Cancer 16 (2009), 325–332.
62. [62] Haffner, M.C., Aryee, M.J., Toubaji, A., Esopi, D.M., Albadine, R., Gurel, B., et al. Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements. Nat Genet 42 (2010), 668–675.
63. [63] Vander Griend, D.J., Litvinov IV, Isaacs, J.T., Stabilizing androgen receptor in mitosis inhibits prostate cancer proliferation. Cell Cycle 6 (2007), 647–651.
64. [64] Schweizer, M.T., Antonarakis, E.S., Wang, H., Ajiboye, A.S., Spitz, A., Cao, H., et al. Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: results from a pilot clinical study. Sci Transl Med, 7, 2015, 269ra2.
65. [65] Kantoff, P.W., Higano, C.S., Shore, N.D., Berger, E.R., Small, E.J., Penson, D.F., et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363 (2010), 411–422.
66. [66] de Bono, J.S., Oudard, S., Ozguroglu, M., Hansen, S., Machiels, J.P., Kocak, I., et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376 (2010), 1147–1154.
67. [67] Parker, C., Nilsson, S., Heinrich, D., Helle, S.I., O׳Sullivan, J.M., Fossa, S.D., et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 369 (2013), 213–223.
68. [68] De Wit R, Fizazi K,Viorel Jinga, et al. Phase 3, randomized, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients (pts) with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) (ELM-PC 4 trial). ASCO Annual Meeting; 2014.
69. [69] Dreicer, R., Jones, R., Oudard, S., Efstathiou, E., Saad, F., De Wit, R., et al. Results from a phase 3, randomized, double-blind, multicenter, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy (ELM-PC 5 trial). ASCO Meeting Abstracts, 32(Suppl. 4), 2014, 7.
70. [70] Sweeney, C., Chen, Y.-H., Carducci, M.A., Liu, G., Jarrard, D.F., Eisenberger, M.A., et al. Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): an ECOG-led phase III randomized trial. ASCO Meeting Abstracts, 32(Suppl. 18), 2014, LBA2.
71. [71] Garcia J. Enzalutamide in patients with high-risk prostate cancer. https://clinicaltrials.gov/ct2/show/NCT01927627; 2015.
72. [72] Templeton, A.J., Dutoit, V., Cathomas, R., Rothermundt, C., Bartschi, D., Droge, C., et al. Phase 2 trial of single-agent everolimus in chemotherapy-naive patients with castration-resistant prostate cancer (SAKK 08/08). Eur Urol 64 (2013), 150–158.
73. [73] Piccart, M., Hortobagyi, G.N., Campone, M., Pritchard, K.I., Lebrun, F., Ito, Y., et al. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2dagger. Ann Oncol 25 (2014), 2357–2362.
74. [74] Finn, R.S., Crown, J.P., Lang, I., Boer, K., Bondarenko, I.M., Kulyk, S.O., et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 16 (2015), 25–35.
75. [75] Tagawa, S.T., Neuroendocrine prostate cancer after hormonal therapy: knowing is half the battle. J Clin Oncol 32 (2014), 3360–3364.
76. [76] Wang, H.T., Yao, Y.H., Li, B.G., Tang, Y., Chang, J.W., Zhang, J., Neuroendocrine Prostate Cancer (NEPC) progressing from conventional prostatic adenocarcinoma: factors associated with time to development of NEPC and survival from NEPC diagnosis-a systematic review and pooled analysis. J Clin Oncol 32 (2014), 3383–3390.
77. [77] Bambury RM, Louw J, Krupa R et al. Characteristics of de novo resistance to androgen targeted therapies through circulating tumors cells analysis in metastatic castration resistant prostate cancer patients. ESMO; 2014; Madrid, Spain.
78. [78] Dittamore R, Krupa R, Louw J, Autio K, Zaina A, Schreiber N, et al. Frequency and characterisation of circulating tumor cell populations in mCRPC. American Association for Cancer Research Annual Meeting; 2014.
79. [79] Hara, T., Miyazaki, J., Araki, H., Yamaoka, M., Kanzaki, N., Kusaka, M., et al. Novel mutations of androgen receptor: a possible mechanism of bicalutamide withdrawal syndrome. Cancer Res 63 (2003), 149–153.
80. [80] Taplin, M.E., Bubley, G.J., Ko, Y.J., Small, E.J., Upton, M., Rajeshkumar, B., et al. Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. Cancer Res 59 (1999), 2511–2515.
81. [81] Cai, C., Chen, S., Ng, P., Bubley, G.J., Nelson, P.S., Mostaghel, E.A., et al. Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors. Cancer Res 71 (2011), 6503–6513.
82. [82] Hu, R., Dunn, T.A., Wei, S., Isharwal, S., Veltri, R.W., Humphreys, E., et al. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res 69 (2009), 16–22.
83. [83] Chen, E., Sowalsky, A.G., Gao, S., Cai, C., Voznesensky, O., Schaefer, R., et al. Abiraterone treatment in castration-resistant prostate cancer selects for progesterone responsive mutant androgen receptors. Clin Cancer Res 21 (2015), 1273–1280.
84. [84] Azad, A.A., Eigl, B.J., Murray, R.N., Kollmannsberger, C., Chi, K.N., Efficacy of enzalutamide following abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer patients. Eur Urol 67 (2015), 23–29.
85. [85] Rathkopf DE, Antonorakis ES, ShoreND, et al. ARN-509 in men with metastatic castration-resistant prostate cancer (mCRPC). ASCO GU Symposium; 2013.