Current Treatment Options in Oncology

, Volume 14, Issue 1, pp 109–126

Novel Therapies for the Treatment of Advanced Prostate Cancer

Genitourinary Cancer (R Pili, Section Editor)

Opinion statement

In recent years, great success has been achieved on many fronts in the treatment of men with metastatic castration-resistant prostate cancer (CRPC), including novel chemotherapeutics, immunotherapies, bone microenvironment-targeted agents, and hormonal therapies. Numerous agents are currently in early-phase clinical trial development for the treatment of advanced prostate cancer. These novel therapies target several areas of prostate tumor biology, including the upregulation of androgen signaling and biosynthesis, critical oncogenic intracellular pathways, epigenetic alterations, and cancer immunology. Importantly, the characterization of the prostate cancer genome offers the potential to exploit conserved genetic alterations, which may increase the efficacy of these targeted therapies. Predictive and prognostic biomarkers are urgently needed to maximize therapeutic efficacy and safety of these promising new treatments options in prostate cancer.


Prostate cancer Novel Treatments Castration-resistant Androgen receptor Metastatic PI3 kinase inhibitors Androgen synthesis inhibitors Immunotherapies Epigenetic Epithelial mesenchymal transition 

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.••
    Grasso CS, Wu YM, Robinson DR, et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012;487:239–43. Characterizes common mutations found in exomes of prostate cancer.PubMedCrossRefGoogle Scholar
  2. 2.••
    Friedlander TW, Roy R, Tomlins SA, et al. Common structural and epigenetic changes in the genome of castration-resistant prostate cancer. Cancer Res. 2012;72:616–25. Describes comprehensive gene methylation and copy number alterations in prostate cancer.PubMedCrossRefGoogle Scholar
  3. 3.••
    Taylor BS, Schultz N, Hieronymus H, et al. Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010;18:11–22. Defines the prostate cancer transcriptome and profile copy number alteration involved in many oncogenic pathways.PubMedCrossRefGoogle Scholar
  4. 4.
    Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.PubMedCrossRefGoogle Scholar
  5. 5.
    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. 2010;376:1147–54.PubMedCrossRefGoogle Scholar
  6. 6.
    de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005.PubMedCrossRefGoogle Scholar
  7. 7.
    Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377:813–22.PubMedCrossRefGoogle Scholar
  8. 8.
    Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012.Google Scholar
  9. 9.
    Chou R, Dana T, Bougatsos C, et al. In: Treatments for localized prostate cancer: systematic review to update the 2002 US preventive services task force recommendation. Rockville (MD); 2011.Google Scholar
  10. 10.
    Lu-Yao GL, Albertsen PC, Moore DF, et al. Outcomes of localized prostate cancer following conservative management. JAMA. 2009;302:1202–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Seidenfeld J, Samson DJ, Hasselblad V, et al. Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med. 2000;132:566–77.PubMedGoogle Scholar
  12. 12.
    Rubin MA, Maher CA, Chinnaiyan AM. Common gene rearrangements in prostate cancer. J Clin Oncol. 2011;29:3659–68.PubMedCrossRefGoogle Scholar
  13. 13.
    Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310:644–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Klezovitch O, Risk M, Coleman I, et al. A causal role for ERG in neoplastic transformation of prostate epithelium. Proc Natl Acad Sci USA. 2008;105:2105–10.PubMedCrossRefGoogle Scholar
  15. 15.
    Cai C, Wang H, Xu Y, Chen S, Balk SP. Reactivation of androgen receptor-regulated TMPRSS2: ERG gene expression in castration-resistant prostate cancer. Cancer Res. 2009;69:6027–32.PubMedCrossRefGoogle Scholar
  16. 16.
    Perner S, Demichelis F, Beroukhim R, et al. TMPRSS2: ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Res. 2006;66:8337–41.PubMedCrossRefGoogle Scholar
  17. 17.
    Mohler JL, Gregory CW, Ford 3rd OH, et al. The androgen axis in recurrent prostate cancer. Clin Cancer Res. 2004;10:440–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Chen CD, Welsbie DS, Tran C, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med. 2004;10:33–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Sarker D, Reid AH, Yap TA, de Bono JS. Targeting the PI3K/AKT pathway for the treatment of prostate cancer. Clin Cancer Res. 2009;15:4799–805.PubMedCrossRefGoogle Scholar
  20. 20.
    Saylor PJ, Armstrong AJ, Fizazi K, et al. New and emerging therapies for bone metastases in genitourinary cancers. Eur Urol 2012.Google Scholar
  21. 21.
    Ryan CJ, Smith MR, De Bono JS, et al. Interim analysis (IA) results of COU-AA-302, a randomized, phase III study of abiraterone acetate (AA) in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). ASCO Meeting Abstracts 2012;30:LBA4518.Google Scholar
  22. 22.
    Tran C, Ouk S, Clegg NJ, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009;324:787–90.PubMedCrossRefGoogle Scholar
  23. 23.
    Clegg NJ, Wongvipat J, Joseph JD, et al. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012;72:1494–503.PubMedCrossRefGoogle Scholar
  24. 24.
    Rathkopf DE DD, Morris MJ, Slovin SF, Steinbrecher JE, Arauz G, Rix PJ, Maneval EC, Chen I, Fox JJ, Fleisher M, Larson SM, Scher HI. Phase I/II safety and pharmacokinetic (PK) study of ARN-509 in patients with metastatic castration-resistant prostate cancer (mCRPC): Phase I results of a Prostate Cancer Clinical Trials Consortium study. J Clin Oncol 2012.Google Scholar
  25. 25.
    Abstract LBA25. In: 2012 European Society for Medical Oncology (ESMO) Congress Presented September 30, 2012; 2012 European Society for Medical Oncology (ESMO) Congress.Google Scholar
  26. 26.•
    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. 2010;17:535–46. Novel mechanism of action in targeting the N-termainal domain of the AR.PubMedCrossRefGoogle Scholar
  27. 27.
    Sadar MD. Small molecule inhibitors targeting the "achilles' heel" of androgen receptor activity. Cancer Res. 2011;71:1208–13.PubMedCrossRefGoogle Scholar
  28. 28.
    Hu R, Lu C, Mostaghel EA, et al. Distinct transcriptional programs mediated by the ligand-dependent full-length androgen receptor and its splice variants in castration-resistant prostate cancer. Cancer Res. 2012;72:3457–62.PubMedCrossRefGoogle Scholar
  29. 29.
    Mostaghel EA, Marck BT, Plymate SR, et al. Resistance to CYP17A1 inhibition with abiraterone in castration-resistant prostate cancer: induction of steroidogenesis and androgen receptor splice variants. Clin Cancer Res. 2011;17:5913–25.PubMedCrossRefGoogle Scholar
  30. 30.
    Stanbrough M, Bubley GJ, Ross K, et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006;66:2815–25.PubMedCrossRefGoogle Scholar
  31. 31.
    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. 2008;68:4447–54.PubMedCrossRefGoogle Scholar
  32. 32.
    Kaku T, Hitaka T, Ojida A, et al. Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. Bioorg Med Chem. 2011;19:6383–99.PubMedCrossRefGoogle Scholar
  33. 33.
    Antonarakis ES, Armstrong AJ. Emerging therapeutic approaches in the management of metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2011;14:206–18.PubMedCrossRefGoogle Scholar
  34. 34.
    Ryan C, Li J, Kheoh T, Scher HI, Molina A. Abstract LB-434: Baseline serum adrenal androgens are prognostic and predictive of overall survival (OS) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC): Results of the COU-AA-301 phase 3 randomized trial. Cancer Res 2012;72:LB-434.Google Scholar
  35. 35.
    Bruno RD, Vasaitis TS, Gediya LK, et al. Synthesis and biological evaluations of putative metabolically stable analogs of VN/124-1 (TOK-001): head to head anti-tumor efficacy evaluation of VN/124-1 (TOK-001) and abiraterone in LAPC-4 human prostate cancer xenograft model. Steroids. 2011;76:1268–79.PubMedCrossRefGoogle Scholar
  36. 36.
    Robert B. Montgomery, Eisenberger MA, Rettig M, Chu F, Pili R, Stephenson J, Vogelzang NJ, Morrison J, Taplin M-E. Phase I clinical trial of galeterone (TOK-001), a multifunctional antiandrogen and CYP17 inhibitor in castration resistant prostate cancer (CRPC). J Clin Oncol 2012.Google Scholar
  37. 37.
    Zoubeidi A, Zardan A, Beraldi E, et al. Cooperative interactions between androgen receptor (AR) and heat-shock protein 27 facilitate AR transcriptional activity. Cancer Res. 2007;67:10455–65.PubMedCrossRefGoogle Scholar
  38. 38.
    Chi KN, Hotte SJ, Ellard S, et al. A randomized phase II study of OGX-427 plus prednisone (P) versus P alone in patients (pts) with metastatic castration resistant prostate cancer (CRPC). ASCO Meeting Abstracts 2012;30:4514.Google Scholar
  39. 39.
    Yakes FM, Chen J, Tan J, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10:2298–308.PubMedCrossRefGoogle Scholar
  40. 40.
    Cecchi F, Rabe DC, Bottaro DP. Targeting the HGF/Met signalling pathway in cancer. Eur J Cancer. 2010;46:1260–70.PubMedCrossRefGoogle Scholar
  41. 41.
    Takayama H, LaRochelle WJ, Sharp R, et al. Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor. Proc Natl Acad Sci USA. 1997;94:701–6.PubMedCrossRefGoogle Scholar
  42. 42.•
    Hussain M, Smith MR, Sweeney C, et al. Cabozantinib (XL184) in metastatic castration-resistant prostate cancer (mCRPC): Results from a phase II randomized discontinuation trial. ASCO Meeting Abstracts 2011;29:4516. Highlights the clinical efficacy of targeting MET in prostate cancer.Google Scholar
  43. 43.
    Smith MR, Sweeney C, Rathkopf DE, et al. Cabozantinib (XL184) in chemotherapy-pretreated metastatic castration resistant prostate cancer (mCRPC): Results from a phase II nonrandomized expansion cohort (NRE). ASCO Meeting Abstracts 2012;30:4513.Google Scholar
  44. 44.••
    Carver BS, Chapinski C, Wongvipat J, et al. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell. 2011;19:575–86. Describes the interplay between PI3K and AR.PubMedCrossRefGoogle Scholar
  45. 45.
    Mulholland DJ, Tran LM, Li Y, et al. Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth. Cancer Cell. 2011;19:792–804.PubMedCrossRefGoogle Scholar
  46. 46.
    Mayer EL, Krop IE. Advances in targeting SRC in the treatment of breast cancer and other solid malignancies. Clin Cancer Res. 2010;16:3526–32.PubMedCrossRefGoogle Scholar
  47. 47.
    Tatarov O, Mitchell TJ, Seywright M, Leung HY, Brunton VG, Edwards J. SRC family kinase activity is up-regulated in hormone-refractory prostate cancer. Clin Cancer Res. 2009;15:3540–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Yu EY, Massard C, Gross ME, et al. Once-daily dasatinib: expansion of phase II study evaluating safety and efficacy of dasatinib in patients with metastatic castration-resistant prostate cancer. Urology. 2011;77:1166–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Araujo JC, Mathew P, Armstrong AJ, et al. Dasatinib combined with docetaxel for castration-resistant prostate cancer: results from a phase 1–2 study. Cancer. 2012;118:63–71.PubMedCrossRefGoogle Scholar
  50. 50.
    Zoubeidi A, Chi K, Gleave M. Targeting the cytoprotective chaperone, clusterin, for treatment of advanced cancer. Clin Cancer Res. 2010;16:1088–93.PubMedCrossRefGoogle Scholar
  51. 51.
    Chi KN, Hotte SJ, Yu EY, et al. Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28:4247–54.PubMedCrossRefGoogle Scholar
  52. 52.
    Saad F, Hotte S, North S, et al. Randomized phase II trial of Custirsen (OGX-011) in combination with docetaxel or mitoxantrone as second-line therapy in patients with metastatic castrate-resistant prostate cancer progressing after first-line docetaxel: CUOG trial P-06c. Clin Cancer Res. 2011;17:5765–73.PubMedCrossRefGoogle Scholar
  53. 53.
    Brenner JC, Ateeq B, Li Y, et al. Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. Cancer Cell. 2011;19:664–78.PubMedCrossRefGoogle Scholar
  54. 54.
    Gulley JL, Drake CG. Immunotherapy for prostate cancer: recent advances, lessons learned, and areas for further research. Clin Cancer Res. 2011;17:3884–91.PubMedCrossRefGoogle Scholar
  55. 55.
    DiPaola RS, Plante M, Kaufman H, et al. A phase I trial of pox PSA vaccines (PROSTVAC-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM) in patients with prostate cancer. J Transl Med. 2006;4:1.PubMedCrossRefGoogle Scholar
  56. 56.
    Kantoff PW, Schuetz TJ, Blumenstein BA, et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28:1099–105.PubMedCrossRefGoogle Scholar
  57. 57.
    May Jr KF, Gulley JL, Drake CG, Dranoff G, Kantoff PW. Prostate cancer immunotherapy. Clin Cancer Res. 2011;17:5233–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Slovin SF, Hamid O, Tejwani S, et al. Ipilimumab (IPI) in metastatic castrate-resistant prostate cancer (mCRPC): Results from an open-label, multicenter phase I/II study. ASCO Meeting Abstracts 2012;30:25.Google Scholar
  59. 59.•
    Dewan MZ, Galloway AE, Kawashima N. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009;15:5379–88. Demonstrates the efficacy of PD-1 inhibition as an effective anti-tumor agent.PubMedCrossRefGoogle Scholar
  60. 60.
    Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28:3167–75.PubMedCrossRefGoogle Scholar
  61. 61.
    Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.PubMedCrossRefGoogle Scholar
  62. 62.
    Kallberg E, Vogl T, Liberg D, et al. S100A9 interaction with TLR4 promotes tumor growth. PLoS One. 2012;7:e34207.PubMedCrossRefGoogle Scholar
  63. 63.
    Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer. 2008;8:618–31.PubMedCrossRefGoogle Scholar
  64. 64.
    Olsson A, Bjork A, Vallon-Christersson J, Isaacs JT, Leanderson T. Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors. Mol Cancer. 2010;9:107.PubMedCrossRefGoogle Scholar
  65. 65.•
    Pili R, Haggman M, Stadler WM, et al. Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer. J Clin Oncol. 2011;29:4022–8. Illustrates importance of manipulating tumor microenvironment.PubMedCrossRefGoogle Scholar
  66. 66.
    Perry AS, Watson RW, Lawler M, Hollywood D. The epigenome as a therapeutic target in prostate cancer. Nat Rev Urol. 2010;7:668–80.PubMedCrossRefGoogle Scholar
  67. 67.
    Berger MF, Lawrence MS, Demichelis F, et al. The genomic complexity of primary human prostate cancer. Nature. 2011;470:214–20.PubMedCrossRefGoogle Scholar
  68. 68.
    Zorn CS, Wojno KJ, McCabe MT, Kuefer R, Gschwend JE, Day ML. 5-aza-2'-deoxycytidine delays androgen-independent disease and improves survival in the transgenic adenocarcinoma of the mouse prostate mouse model of prostate cancer. Clin Cancer Res. 2007;13:2136–43.PubMedCrossRefGoogle Scholar
  69. 69.
    Welsbie DS, 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;69:958–66.PubMedCrossRefGoogle Scholar
  70. 70.
    Bradley D, Rathkopf D, Dunn R, et al. Vorinostat in advanced prostate cancer patients progressing on prior chemotherapy (National Cancer Institute Trial 6862): trial results and interleukin-6 analysis: a study by the Department of Defense Prostate Cancer Clinical Trial Consortium and University of Chicago Phase 2 Consortium. Cancer. 2009;115:5541–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Ferrari AC, Stein MN, Alumkal JJ, et al. A phase I/II randomized study of panobinostat and bicalutamide in castration-resistant prostate cancer (CRPC) patients progressing on second-line hormone therapy. ASCO Meeting Abstracts 2011;29:156.Google Scholar
  72. 72.
    Rathkopf D, Wong BY, Ross RW, et al. A phase I study of oral panobinostat alone and in combination with docetaxel in patients with castration-resistant prostate cancer. Cancer Chemother Pharmacol. 2010;66:181–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Sonpavde G, Aparicio AM, Delaune R, et al. Azacitidine for castration-resistant prostate cancer progressing on combined androgen blockade. ASCO Meeting Abstracts 2008;26:5172.Google Scholar
  74. 74.
    Verheul HM, Qian DZ, Carducci MA, Pili R. Sequence-dependent antitumor effects of differentiation agents in combination with cell cycle-dependent cytotoxic drugs. Cancer Chemother Pharmacol. 2007;60:329–39.PubMedCrossRefGoogle Scholar
  75. 75.
    Armstrong AJ, Marengo MS, Oltean S, et al. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res. 2011;9:997–1007.PubMedCrossRefGoogle Scholar
  76. 76.
    Sun Y, Wang BE, Leong KG, et al. Androgen deprivation causes epithelial-mesenchymal transition in the prostate: implications for androgen-deprivation therapy. Cancer Res. 2012;72:527–36.PubMedCrossRefGoogle Scholar
  77. 77.
    Kottke T, Errington F, Pulido J, et al. Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors. Nat Med. 2011;17:854–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.PubMedCrossRefGoogle Scholar
  79. 79.
    Gupta PB, Onder TT, Jiang G, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138:645–59.PubMedCrossRefGoogle Scholar
  80. 80.
    Sun Y, Campisi J, Higano C, et al. Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat Med 2012.Google Scholar
  81. 81.
    Mulholland DJ, Kobayashi N, Ruscetti M, et al. Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells. Cancer Res. 2012;72:1878–89.PubMedCrossRefGoogle Scholar
  82. 82.
    Shiota M, Zardan A, Takeuchi A, et al. Clusterin mediates TGF-beta-induced epithelial-mesenchymal transition and metastasis via Twist1 in prostate cancer cells. Cancer Res 2012.Google Scholar
  83. 83.
    Wu K, Zeng J, Li L, et al. Silibinin reverses epithelial-to-mesenchymal transition in metastatic prostate cancer cells by targeting transcription factors. Oncol Rep. 2010;23:1545–52.PubMedCrossRefGoogle Scholar
  84. 84.
    Tanaka H, Kono E, Tran CP, et al. Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance. Nat Med. 2010;16:1414–20.PubMedCrossRefGoogle Scholar
  85. 85.
    Singh RP, Raina K, Sharma G, Agarwal R. Silibinin inhibits established prostate tumor growth, progression, invasion, and metastasis and suppresses tumor angiogenesis and epithelial-mesenchymal transition in transgenic adenocarcinoma of the mouse prostate model mice. Clin Cancer Res. 2008;14:7773–80.PubMedCrossRefGoogle Scholar
  86. 86.
    LoRusso PM, Rudin CM, Reddy JC, et al. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res. 2011;17:2502–11.PubMedCrossRefGoogle Scholar
  87. 87.
    Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366:2171–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Domingo-Domenech J, Vidal SJ, Rodriguez-Bravo V, et al. Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells. Cancer Cell. 2012;22:373–88.PubMedCrossRefGoogle Scholar
  89. 89.
    Kelly WK, Halabi S, Carducci M, et al. Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401. J Clin Oncol. 2012;30:1534–40.PubMedCrossRefGoogle Scholar
  90. 90.
    Ou Y, Michaelson MD, Sengelov L, et al. Randomized, placebo-controlled, phase III trial of sunitinib in combination with prednisone (SU + P) versus prednisone (P) alone in men with progressive metastatic castration-resistant prostate cancer (mCRPC). ASCO Meeting Abstracts 2011;29:4515.Google Scholar
  91. 91.
    Agarwal N, Sonpavde G, Sternberg CN. Novel molecular targets for the therapy of castration-resistant prostate cancer. Eur Urol. 2012;61:950–60.PubMedCrossRefGoogle Scholar
  92. 92.
    Armstrong AJ, Eisenberger MA, Halabi S, et al. Biomarkers in the management and treatment of men with metastatic castration-resistant prostate cancer. Eur Urol. 2012;61:549–59.PubMedCrossRefGoogle Scholar
  93. 93.
    Bryant RJ, Pawlowski T, Catto JW, et al. Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer. 2012;106:768–74.PubMedCrossRefGoogle Scholar
  94. 94.•
    Armstrong AJ, George DJ, Halabi S. Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of Mammalian target of rapamycin. J Clin Oncol. 2012;30:3402–7. First predictive biomarker in GU oncology.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Duke Cancer Institute and the Duke Prostate Center, Department of Medicine, Division of Medical OncologyDuke University Medical CenterDurhamUSA

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