Resistance to Castration – Resistance to Drugs

Chapter

Abstract

Up to 70 % of newly diagnosed patients with advanced prostate cancer (PCa) will progress to castration-resistant prostate cancer (CRPC) and, in most cases (from 50 to 70 %), will develop hematogenous bone metastasis. Once PCa cells spread to the skeleton, cancer-related death becomes inevitable, with a death burden of more than 28,000 cases in 2012, in the United States (Semenas et al, Curr Drug Target, 13(10):1308–1323, 2012).

To date, therapeutic regimens are unable to revert this fatal progression (Semenas et al, Curr Drug Target, 13(10):1308–1323, 2012).

Thus, PCa bone metastatic prostate cancer still represents a major clinical challenge.

Prostate cancer biology is tightly linked to AR, which regulates epithelial proliferation and suppresses apoptosis both in normal and in cancer prostate tissue, and is involved in the progression of the disease toward a castration-resistant state (Hodgson et al, World J Urol, 30(3):279–285, 2012). Our knowledge of the molecular mechanisms, responsible for the acquired resistance to ADT in prostate cancer, has exponentially progressed during the last years. For instance, we have recently learnt that it may be associated with the occurrence of AR splicing variants (Hu et al. 2011).

Surgical castration has shown to induce regression of advanced disease 40-years before the cloning of androgen receptor (AR) (Huggins et al, Arch Surg, 43:209–223, 1941; Lubahn et al, Science, 240:327–330, 1988).

Since then, hormonal therapy was held over as the main available therapeutic option for aggressive prostate cancers. In the last decade, however, chemotherapy was introduced to targeting the epithelium of metastatic, hormone-resistant prostate cancer (Pinto et al, Tumour Biol, 33(2):421–426, 2012; Hodgson et al, World J Urol, 30(3):279–285, 2012). The cytotoxic conventional drug Docetaxel was approved by the Food and Drug Administration in 2004, and still represents the standard first-line treatment for patients with castration-resistant prostate cancer (CRPC) (Sartor et al, Oncologist, 16(11):1487–1497, 2011). It produces sensible palliative effects on bone-metastasis-related symptoms, but prolongs only modestly the survival of patients (Hodgson et al, World J Urol, 30(3):279–285, 2012; Tannock et al, N Engl J Med, 351:1502–1512, 2004; Petrylak et al, N Engl J Med, 351:1513–1520, 2004). Docetaxel acts mainly by inducing apoptosis of target epithelial cells. The common intrinsic defects of mCRPC in apoptosis pathways, such as BCL-2 overexpression and/or phosphatase and tensin homolog (PTEN) loss (Mathew, Dipaola, J Urol, 178:S36–S41, 2007; Galsky, Vogelzang, Ann Oncol, 21:2135–2144, 2010), may constitute the rationale of the unsatisfactory rate of cure attributable to this drug (Srigley et al, Histopathology, 60(1):153–165, 2012). In recent years, similar effects on survival have been demonstrated also for several other chemotherapeutic agents, such as mitoxantrone, etoposide, cisplatinum, vinblastine–estramustine and taclitaxel.

Following progression after treatment with docetaxel, new cabazitaxel (XRP6258)-prednisone treatment regimens have led to a significantly longer overall survival, and other novel agents are currently being evaluated, including the cell-based immunotherapy sipuleucel-T, the androgen biosynthesis inhibitors abiraterone acetate and MDV3100, the chemotherapic Cabazitaxel, as well as the radionuclide alpharadin/Radium 223 (bone microenvironment targeting agents) (Sartor et al, Oncologist, 16(11):1487–1497, 2011; Liu et al, Front Endocrinol (Lausanne), 3:72, 2012; Antonarakis, Armstrong, Prostate Cancer Prostatic Dis, 14(3):206–218, 2011). To date, they seem to offer a survival advantage to patients, and look promising to improve the prognosis of metastatic CRPC.

However, the real clinical benefit of these systemic therapies remains still transient, probably due also to the well-known clonal heterogeneity of advanced prostate cancers, and the overall survival of patients that holds frustratingly steady.

The high cost of these therapies and the increasing complexity of clinical decision making, further underscore the need to multiply the efforts to develop more potent chemotherapy agents and/or novel AR/inhibitors agents that may better overcome resistance mechanisms to existing therapies (Liu et al, Front Endocrinol (Lausanne), 2012; Hodgson et al, World J Urol, 30(3):279–285, 2012; Armstrong, George, Urol Oncol, 26:430–437, 2008; Schrijvers et al, Adv Ther, 27:285–296, 2010).

Several recently developed drug candidates, directed against the metastatic cancer microenvironments or niches, show promising results in this direction (Hodgson et al, World J Urol, 30(3):279–285, 2012).

The efficacy of the standard-of-care therapeutic intervention directed to mCRPC will be greatly improved by our increasing understanding of molecular mechanisms of the acquired resistance to ADT and chemotherapy, which is expected to provide valuable insights also to new unfailing biomarkers of resistance, therapeutic response and disease progression of prostate cancer, allowing us to personalize the therapy for the single patients with mCRPC (Liu et al, Front Endocrinol (Lausanne), 3:72, 2012; Antonarakis and Armstrong, Prostate Cancer Prostatic Dis, 14(3):206–218, 2011).

The knowledge of the molecular mechanisms underpinning prostate cancer progression is changing dramatically our therapeutic approach to its advanced, metastasizing phase, opening up the chance to design and develop novel agents targeting the multiple pathways responsible for the lethal cancer phenotype, in a more efficient and safer manner (Corcoran and Gleave, Histopathology, 60(1): 216–231, 2012).

Keywords

Prostate Cancer Androgen Receptor Prostate Cancer Cell Androgen Deprivation Therapy Advanced Prostate Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Agarwal N, Sonpavde G, Sternberg CN (2012) Novel molecular targets for the therapy of castration-resistant prostate cancer. Eur Urol 61(5):950–960. Epub 2011 Dec 22PubMedCrossRefGoogle Scholar
  2. Antolín AR, Ojeda JM, Otero JR, Rodríguez AC, Castellano D, Esteban MD, Sicilia LD, González RD (2012) Hormonal treatment in biochemical recurrence after radical prostatectomy. Arch Esp Urol 65(1):111–121. Review. SpanishPubMedGoogle Scholar
  3. Antonarakis ES, Armstrong AJ (2011) Emerging therapeutic approaches in the management of metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 14(3):206–218. Epub 2011 May 17. ReviewPubMedCrossRefGoogle Scholar
  4. Araujo J, Logothetis C (2010) Dasatinib: a potent SRC inhibitor in clinical development for the treatment of solid tumors. Cancer Treat Rev 36:492–500PubMedCrossRefGoogle Scholar
  5. Armas OA, Aprikian AG, Melamed J et al (1994) Clinical and pathological effects of neoadjuvant total androgen ablation therapy on clinically localized prostatic adenocarcinoma. Am J Surg Pathol 18:979–991PubMedCrossRefGoogle Scholar
  6. Armstrong AJ, George DJ (2008) New drug development in metastatic prostate cancer. Urol Oncol 26:430–437PubMedCrossRefGoogle Scholar
  7. Batist G (2007) Cardiac safety of liposomal anthracyclines. Cardiovasc Toxicol 7:72–74PubMedCrossRefGoogle Scholar
  8. Beekman KW, Hussain M (2008) Hormonal approaches in prostate cancer: application in the contemporary prostate cancer patient. Urol Oncol 26(4):415–419PubMedCrossRefGoogle Scholar
  9. Beer TM, Garzotto M, Henner WD, Eilers KM, Wersinger EM (2004) Multiple cycles of intermittent chemotherapy in metastatic androgen-independent prostate cancer. Br J Cancer 91:1425–1427PubMedGoogle Scholar
  10. Berthold DR, Sternberg CN, Tannock IF (2005) Management of advanced prostate cancer after first-line chemotherapy. J Clin Oncol 23:8247–8252PubMedCrossRefGoogle Scholar
  11. Bradley DA, Hussain M (2008) Promising novel cytotoxic agents and combinations in metastatic prostate cancer. Cancer J 14(1):15–19. ReviewPubMedCrossRefGoogle Scholar
  12. Bullock MJ, Srigley JR, Klotz LH et al (2002) Pathologic effects of neoadjuvant cyproterone acetate on nonneoplastic prostate, prostatic intraepithelial neoplasia, and adenocarcinoma. A detailed analysis of radical prostatectomy specimens from a randomized trial. Am J Surg Pathol 26:1400–1413PubMedCrossRefGoogle Scholar
  13. Carducci MA, Saad F, Abrahamsson PA et al (2007) A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Cancer 110:1959–1966PubMedCrossRefGoogle Scholar
  14. Chi KN, Zoubeidi A, Gleave ME (2008) Custirsen (OGX-011): a second-generation antisense inhibitor of clusterin for the treatment of cancer. Expert Opin Investig Drug 17:1955–1962CrossRefGoogle Scholar
  15. Chodak G, Sharifi R, Kasimis B, Block NL, Macramalla E, Kennealey GT (1995) Single-agent therapy with bicalutamide: a comparison with medical or surgical castration in the treatment of advanced prostate carcinoma. Urology 46(6):849–855PubMedCrossRefGoogle Scholar
  16. Civantos F, Marcial MA, Banks ER et al (1995) Pathology of androgen deprivation therapy in prostate carcinoma: a comparative study of 173 patients. Cancer 75:1634–1641PubMedCrossRefGoogle Scholar
  17. Cook RJ, Coleman R, Brown J et al (2006) Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer. Clin Cancer Res 12:3361–3367PubMedCrossRefGoogle Scholar
  18. Corcoran NM, Gleave ME (2012) Targeted therapy in prostate cancer. Histopathology 60(1):216–231PubMedCrossRefGoogle Scholar
  19. de Bono JS, Oudard S, Ozguroglu M et al (2010) Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376:1147–1154PubMedCrossRefGoogle Scholar
  20. Debes JD, Tindall DJ (2004) Mechanisms of androgen-refractory prostate cancer. N Engl J Med 351(15):1488–1490PubMedCrossRefGoogle Scholar
  21. Dias-Santagata D, Akhavanfardy S, David SS, Vernovsky K, Kuhlmann G, Boisvert SL, Stubbs H, McDermott U, Settleman J, Kwak EL, Clark JW, Isakoff SJ, Sequist LV, Engelman JA, Lynch TJ, Haber DA, Louis DN, Ellisen LW, Borger DR, John A (2010) Iafrate Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine. EMBO Mol Med 2:146–158PubMedCrossRefGoogle Scholar
  22. El-Amm J, Aragon-Ching JB (2013) The changing landscape in the treatment of metastatic castration-resistant prostate cancer. Ther Adv Med Oncol 5(1):25–40PubMedCrossRefGoogle Scholar
  23. el-Rayes BF, Hussain MH (2002) Hormonal therapy for prostate cancer: past, present and future. Expert Rev Anticancer Ther 2(1):37–47PubMedCrossRefGoogle Scholar
  24. Evans AJ, Ryan P, van der Kwast T (2011) Treatment effects in the prostate including those associated with traditional and emerging therapies. Adv Anat Pathol 18:281–293PubMedCrossRefGoogle Scholar
  25. Ewer MS, Martin FJ, Henderson C, Shapiro CL, Benjamin RS, Gabizon AA (2004) Cardiac safety of liposomal anthracyclines. Semin Oncol 31:161–181PubMedCrossRefGoogle Scholar
  26. Feldman BJ, Feldman D (2001) The development of androgen-independent prostate cancer. Nat Rev Cancer 1(1):34–45. ReviewPubMedCrossRefGoogle Scholar
  27. Fizazi K, Carducci M, Smith M et al (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377:813–882PubMedCrossRefGoogle Scholar
  28. Gabizon A, Shmeeda H, Barenholz Y (2003) Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies. Clin Pharmacokinet 42:419–436PubMedCrossRefGoogle Scholar
  29. Galsky MD, Vogelzang NJ (2010) Docetaxel-based combination therapy for castration-resistant prostate cancer. Ann Oncol 21:2135–2144PubMedCrossRefGoogle Scholar
  30. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892. Erratum in: N Engl J Med. 2012 Sep 6;367(10):976PubMedCrossRefGoogle Scholar
  31. Gleave ME, Miyake H, Zellweger T et al (2001) Use of antisense oligonucleotides targeting the antiapoptotic gene, clusterin/testosterone-repressed prostate message 2, to enhance androgen sensitivity and chemosensitivity in prostate cancer. Urology 58:39–49PubMedCrossRefGoogle Scholar
  32. Growcott JW (2009) Preclinical anticancer activity of the specific endothelin A receptor antagonist ZD4054. Anticancer Drug 20:83–88CrossRefGoogle Scholar
  33. Guise TA, Yin JJ, Mohammad KS (2003) Role of endothelin-1 in osteoblastic bone metastases. Cancer 97:779–784PubMedCrossRefGoogle Scholar
  34. Hodgson MC, Bowden WA, Agoulnik IU (2012) Androgen receptor footprint on the way to prostate cancer progression. World J Urol 30(3):279–285. Epub 2011 Sep 17. ReviewPubMedCrossRefGoogle Scholar
  35. Hu R, Isaacs WB, Luo J (2011) A snapshot of the expression signature of androgen receptor splicing variants and their distinctive transcriptional activities. Prostate. 71(15):1656–1667Google Scholar
  36. Huggins C, Hodges CV (1941) Studies on prostatic cancer: (1) the effect of estrogen and of androgen injection on serum phosphates in metastatic carcinoma of the prostate. Cancer Res 1:293–297Google Scholar
  37. Huggins C, Stevens RE, Hodges CV (1941) Studies on prostatic cancer: (II) the effects of castration on advanced carcinoma of the prostate gland. Arch Surg 43:209–223CrossRefGoogle Scholar
  38. Humphrey PA (2003) Prostate pathology. American Society for Clinical Pathology, Chicago, pp 456–476Google Scholar
  39. July LV, Akbari M, Zellweger T, Jones EC, Goldenberg SL, Gleave ME (2002) Clusterin expression is significantly enhanced in prostate cancer cells following androgen withdrawal therapy. Prostate 50:179–188PubMedCrossRefGoogle Scholar
  40. Koukourakis MI, Koukouraki S, Giatromanolaki A, Kakolyris S, Georgoulias V, Velidaki A, Archimandritis S, Karkavitsas NN (2000) High intratumoral accumulation of stealth liposomal doxorubicin in sarcomas–rationale for combination with radiotherapy. Acta Oncol 39:207–211PubMedCrossRefGoogle Scholar
  41. Langenhuijsen JF, Badhauser D, Schaaf B, Kiemeney LA, Witjes JA, Mulders PF (2013) Continuous vs. intermittent androgen deprivation therapy for metastatic prostate cancer. Urol Oncol. 31(5):549–556Google Scholar
  42. Lee LF, Guan J, Qiu Y, Kung HJ (2001) Neuropeptide-induced androgen independence in prostate cancer cells: roles of nonreceptor tyrosine kinases Etk⁄Bmx, Src, and focal adhesion kinase. Mol Cell Biol 21:8385–8397PubMedCrossRefGoogle Scholar
  43. Lee LF, Louie MC, Desai SJ et al (2004) Interleukin-8 confers androgenindependent growth and migration of LNCaP: differential effects of tyrosine kinases Src and FAK. Oncogene 23:2197–2205PubMedCrossRefGoogle Scholar
  44. Liu Y, Hegde P, Zhang F, Hampton G, Jia S (2012) Prostate cancer – a biomarker perspective. Front Endocrinol (Lausanne) 3:72Google Scholar
  45. Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS, Wilson EM (1988) Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 240:327–330PubMedCrossRefGoogle Scholar
  46. Mathew P, Dipaola R (2007) Taxane refractory prostate cancer. J Urol 178:S36–S41PubMedCrossRefGoogle Scholar
  47. Mathew P, Thall PF, Bucana CD et al (2007) Platelet-derived growth factor receptor inhibition and chemotherapy for castration-resistant prostate cancer with bone metastases. Clin Cancer Res 13:5816–5824PubMedCrossRefGoogle Scholar
  48. Mita AC, Denis LJ, Rowinsky EK et al (2009) Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1-hour infusion every 3 weeks in patients with advanced solid tumors. Clin Cancer Res 15:723–730PubMedCrossRefGoogle Scholar
  49. Miyake H, Nelson C, Rennie PS, Gleave ME (2000) Testosterone-repressed prostate message-2 is an antiapoptotic gene involved in progression to androgen independence in prostate cancer. Cancer Res 60:170–176PubMedGoogle Scholar
  50. Mohler JL (2008) A role for the androgen-receptor in clinically localized and advanced prostate cancer. Best Pract Res Clin Endocrinol Metab 22(2):357–372. ReviewPubMedCrossRefGoogle Scholar
  51. Montgomery RB, Mostaghel EA, Vessella R et al (2008) Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res 68:4447–4454PubMedCrossRefGoogle Scholar
  52. Morote J, Orsola A, Planas J, Trilla E, Raventós CX, Cecchini L, Catalán R (2007) Redefining clinically significant castration levels in patients with prostate cancer receiving continuous androgen deprivation therapy. J Urol 178(4 Pt 1):1290–1295PubMedCrossRefGoogle Scholar
  53. Mostaghel EA, Montgomery B, Nelson PS (2009) Castration-resistant prostate cancer: targeting androgen metabolic pathways in recurrent disease. Urol Oncol 27(3):251–257Google Scholar
  54. NCCN (National Comprehensive Cancer Network) (2011) Guidelines for Patientes. Proste cancer, Version 1Google Scholar
  55. Nelson JB, Chan-Tack K, Hedican SP et al (1996) Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer. Cancer Res 56:663–668PubMedGoogle Scholar
  56. Nelson J, Bagnato A, Battistini B, Nisen P (2003) The endothelin axis: emerging role in cancer. Nat Rev Cancer 3:110–116PubMedCrossRefGoogle Scholar
  57. Park SI, Shah AN, Zhang J, Gallick GE (2007) Regulation of angiogenesis and vascular permeability by Src family kinases: opportunities for therapeutic treatment of solid tumors. Expert Opin Ther Target 11:1207–1217CrossRefGoogle Scholar
  58. Park SI, Zhang J, Phillips KA et al (2008) Targeting SRC family kinases inhibits growth and lymph node metastases of prostate cancer in an orthotopic nude mouse model. Cancer Res 68:3323–3333PubMedCrossRefGoogle Scholar
  59. Petraki CD, Sfikas CP (2007) Histopathological changes induced by therapies in the benign prostate and prostate adenocarcinoma. Histol Histopathol 1:107–118Google Scholar
  60. Petrylak DP, Tangen CM, Hussain MH et al (2004) Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351:1513–1520PubMedCrossRefGoogle Scholar
  61. Pienta KJ, Bradley D (2006) Mechanisms underlying the development of androgen-independent prostate cancer. Clin Cancer Res 12(6):1665–1671PubMedCrossRefGoogle Scholar
  62. Pinto A, Merino M, Zamora P, Redondo A, Castelo B, Espinosa E (2012) Targeting the endothelin axis in prostate carcinoma. Tumour Biol 33(2):421–426. Epub 2011 Dec 29PubMedCrossRefGoogle Scholar
  63. Saad F, Gleason DM, Murray R et al (2002) A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 94:1458–1468PubMedCrossRefGoogle Scholar
  64. Sartor O, Michels RM, Massard C, de Bono JS (2011) Novel therapeutic strategies for metastatic prostate cancer in the post-docetaxel setting. Oncologist 16(11):1487–1497. Epub 2011 Nov 2.ReviewPubMedCrossRefGoogle Scholar
  65. Scher HI, Sawyers CL (2005) Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J Clin Oncol 23:8253–8261PubMedCrossRefGoogle Scholar
  66. Scher HI, Liebertz C, Kelly WK, Mazumdar M, Brett C, Schwartz L, Kolvenbag G, Shapiro L, Schwartz M (1997) Bicalutamide for advanced prostate cancer: the natural versus treated history of disease. J Clin Oncol 15(8):2928–2938PubMedGoogle Scholar
  67. Schrijvers D, Van Erps P, Cortvriend J (2010) Castration-refractory prostate cancer: new drugs in the pipeline. Adv Ther 27:285–296PubMedCrossRefGoogle Scholar
  68. Schwarz EM, Ritchlin CT (2007) Clinical development of anti-RANKL therapy. Arthritis Res Ther 9(suppl 1):S7PubMedCrossRefGoogle Scholar
  69. Semenas J, Allegrucci C, Boorjian SA, Mongan NP, Persson JL (2012) Overcoming drug resistance and treating advanced prostate cancer. Curr Drug Target 13(10):1308–1323. ReviewCrossRefGoogle Scholar
  70. Srigley JR, Delahunt B, Evans AJ (2012) Therapy-associated effects in the prostate gland. Histopathology 60(1):153–165PubMedCrossRefGoogle Scholar
  71. Sun Y, Campisi J, Higano C, Beer TM, Porter P, Coleman I, True L, Nelson PS (2012) Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat Med 18(9):1359–1368PubMedCrossRefGoogle Scholar
  72. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA (2004) TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351(15):1502–1512PubMedCrossRefGoogle Scholar
  73. Taplin ME (2008) Androgen receptor: role and novel therapeutic prospects in prostate cancer. Expert Rev Anticancer Ther 8(9):1495–1508. ReviewPubMedCrossRefGoogle Scholar
  74. Têtu B (2008) Morphological changes induced by androgen blockade in normal prostate and prostatic carcinoma. Best Pract Res Clin Endocrinol Metab 22:271–283PubMedCrossRefGoogle Scholar
  75. Têtu B, Srigley JR, Boivin JC et al (1991) Effect of combination endocrine therapy (LHRH agonist and flutamide) on normal prostate and prostatic adenocarcinoma. A histopathologic and immunohistochemical study. Am J Surg Pathol 15:111–120PubMedCrossRefGoogle Scholar
  76. Tiligada E, Miligkos V, Delitheos A (2002) Cross-talk between cellular stress, cell cycle and anticancer agents: mechanistic aspects. Curr Med Chem Anticancer Agent 2:553–566CrossRefGoogle Scholar
  77. Tyrrell CJ, Payne H, See WA, McLeod DG, Wirth MP, Iversen P, Armstrong J, Morris C (2005) Casodex’ Early Prostate Cancer Trialists Group. Bicalutamide (‘Casodex’) 150 mg as adjuvant to radiotherapy in patients with localised or locally advanced prostate cancer: results from the randomised Early Prostate Cancer Programme. Radiother Oncol 76(1):4–10PubMedCrossRefGoogle Scholar
  78. Vallancourt L, Têtu B, Fradet Y et al (1996) Effect of neoadjuvant endocrine therapy (combined androgen blockade) on normal prostate and prostatic carcinoma: a randomized study. Am J Surg Pathol 20:86–93CrossRefGoogle Scholar
  79. Zellweger T, Miyake H, July LV, Akbari M, Kiyama S, Gleave ME (2001) Chemosensitization of human renal cell cancer using antisense oligonucleotides targeting the antiapoptotic gene clusterin. Neoplasia 3:360–367PubMedCrossRefGoogle Scholar
  80. Zellweger T, Chi K, Miyake H et al (2002) Enhanced radiation sensitivity in prostate cancer by inhibition of the cell survival protein clusterin. Clin Cancer Res 8:3276–3284PubMedGoogle Scholar
  81. Zoubeidi A, Chi K, Gleave M (2010) Targeting the cytoprotective chaperone, clusterin, for treatment of advanced cancer. Clin Cancer Res 16:1088–1093PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Advanced Biomedical Sciences, Pathology Section, Faculty of Medicine and SurgeryUniversity of Naples “Federico II”NaplesItaly

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