Cell mates: Paracrine and stromal targets for prostate cancer therapy

Nature Reviews Urology

Volumn 10, Issue 8, 2013, Pages 441-451

  Sluka, Pavel ^a   Davis, Ian D ^a  

^a MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ABIRATERONE; ABIRATERONE ACETATE; AFLIBERCEPT; ANDROGEN RECEPTOR; BEVACIZUMAB; CABOZANTINIB; CETUXIMAB; CHEMOKINE; CYTOKINE; DENOSUMAB; DOCETAXEL; ENZALUTAMIDE; EPHRIN A5; EPHRIN B2; FIBROBLAST GROWTH FACTOR; GALETERONE; GEFITINIB; LAPATINIB; ORTERONEL; OSTEOCLAST DIFFERENTIATION FACTOR; PREDNISONE; SIPULEUCEL T; SONIC HEDGEHOG PROTEIN; SORAFENIB; SUNITINIB; TRASTUZUMAB; VASCULOTROPIN; ZIBOTENTAN; ZOLEDRONIC ACID;

ANDROGEN SYNTHESIS; ANTIANGIOGENIC ACTIVITY; BONE METASTASIS; CANCER CELL; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER SURVIVAL; CASTRATION RESISTANT PROSTATE CANCER; CIRCULATING TUMOR CELL; CLINICAL TRIAL (TOPIC); EPITHELIAL MESENCHYMAL TRANSITION; EPITHELIUM CELL; FIBROBLAST; HUMAN; IMMUNE SYSTEM; MOLECULARLY TARGETED THERAPY; OVERALL SURVIVAL; PARACRINE SIGNALING; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; QUALITY OF LIFE; REVIEW; STROMA CELL; SYSTEMIC THERAPY; TARGET CELL;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DELIVERY SYSTEMS; HUMANS; MALE; PARACRINE COMMUNICATION; PROSTATIC NEOPLASMS; STROMAL CELLS;

EID: 84881613770     PISSN: 17594812     EISSN: 17594820     Source Type: Journal    
DOI: 10.1038/nrurol.2013.146     Document Type: Review

References (136)

1. Siegel, R., Naishadham, D. & Jemal, A. Cancer statistics, 2012. CA Cancer J. Clin. 62, 10-29 (2012).
2. Petrylak, D. P. et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N. Engl. J. Med. 351, 1513-1520 (2004).
3. Tannock, I. F. et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N. Engl. J. Med. 351, 1502-1512 (2004).
4. Liao, C. P., Adisetiyo, H., Liang, M. & Roy-Burman, P. Cancer-associated fibroblasts enhance the gland-forming capability of prostate cancer stem cells. Cancer Res. 70, 7294-7303 (2010).
5. Berry, P. A., Maitland, N. J. & Collins, A. T. Androgen receptor signalling in prostate: effects of stromal factors on normal and cancer stem cells. Mol. Cell. Endocrinol. 288, 30-37 (2008).
6. Maitland, N. J. & Collins, A. T. Prostate cancer stem cells: a new target for therapy. J. Clin. Oncol. 26, 2862-2870 (2008).
7. Gingrich, J. R. et al. Metastatic prostate cancer in a transgenic mouse. Cancer Res. 56, 4096-4102 (1996).
8. Suraneni, M. V. et al. Transgenic expression of 15-lipoxygenase 2 (15-LOX2) in mouse prostate leads to hyperplasia and cell senescence. Oncogene 29, 4261-4275 (2010).
9. Corey, E. & Vessella, R. in Prostate Cancer (eds Chung, L. K., Isaacs, W. & Simons, J.) 3-31 (Humana Press, 2007).
10. Giannoni, E. et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res. 70, 6945-6956 (2010).
11. de Bono, J. S. 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).
12. Agarwal, N., Sonpavde, G. & Sternberg, C. N. Novel molecular targets for the therapy of castration-resistant prostate cancer. Eur. Urol. 61, 950-960 (2012).
13. Galsky, M. D., Small, A. C., Tsao, C. K. & Oh, W. K. Clinical development of novel therapeutics for castration-resistant prostate cancer: historic challenges and recent successes. CA Cancer J. Clin. 62, 299-308 (2012).
14. Barrie, S. E. et al. Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase). J. Steroid Biochem. Mol. Biol. 50, 267-273 (1994).
15. Montgomery, R. B. et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res. 68, 4447-4454 (2008).
16. de Bono, J. S. et al. Abiraterone and increased survival in metastatic prostate cancer. N. Engl. J. Med. 364, 1995-2005 (2011).
17. Fizazi, K. et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 13, 983-992 (2012).
18. Ryan, C. J. et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N. Engl. J. Med. 368, 138-148 (2013).
19. Reid, A. H. et al. Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J. Clin. Oncol. 28, 1489-1495 (2010).
20. Tran, C. et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324, 787-790 (2009).
21. Scher, H. I. et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N. Engl. J. Med. 367, 1187-1197 (2012).
22. US National Library of Medicine. ClinicalTrials.gov [online], http://clinicaltrials.gov/show/NCT01212991 (2013).
23. Kantoff, P. W. et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363, 411-422 (2010).
24. Wolchok, J. D. et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin. Cancer Res. 15, 7412-7420 (2009).
25. Lacey, D. L. et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93, 165-176 (1998).
26. Fizazi, K. et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377, 813-822 (2011).
27. Smith, M. R. et al. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 379, 39-46 (2012).
28. Kelly, W. K. 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. 30, 1534-1540 (2012).
29. Aragon-Ching, J. B. et al. Final analysis of a phase II trial using sorafenib for metastatic castration-resistant prostate cancer. BJU Int. 103, 1636-1640 (2009).
30. Sonpavde, G. et al. Sunitinib malate for metastatic castration-resistant prostate cancer following docetaxel-based chemotherapy. Ann. Oncol. 21, 319-324 (2010).
31. Nelson, J. B. et al. Phase 3, randomized, placebo-controlled study of zibotentan (ZD4054) in patients with castration-resistant prostate cancer metastatic to bone. Cancer 118, 5709-5718 (2012).
32. Tannock, I. et al. Aflibercept versus placebo in combination with docetaxel/prednisone for first-line treatment of men with metastatic castration-resistant prostate cancer (mCRPC): results from the multinational phase III trial (VENICE). J. Clin. Oncol. 31 (Suppl. 6), a13 (2013).
33. Mardjuadi, F. et al. Phase I study of sorafenib in combination with docetaxel and prednisone in chemo-naive patients with metastatic castration-resistant prostate cancer. Cancer Chemother. Pharmacol. 70, 293-303 (2012).
34. Ning, Y. M. et al. Phase II trial of bevacizumab, thalidomide, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer. J. Clin. Oncol. 28, 2070-2076 (2010).
35. Keizman, D. et al. Lenalidomide in nonmetastatic biochemically relapsed prostate cancer: results of a phase I/II double-blinded, randomized study. Clin. Cancer Res. 16, 5269-5276 (2010).
36. Pili, R. 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. 29, 4022-4028 (2011).
37. Aftab, D. T. & McDonald, D. M. MET and VEGF: synergistic targets in castration-resistant prostate cancer. Clin. Transl. Oncol. 13, 703-709 (2011).
38. Verras, M. et al. The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression. Cancer Res. 67, 967-975 (2007).
39. Tu, W. H., Zhu, C., Clark, C., Christensen, J. G. & Sun, Z. Efficacy of c-Met inhibitor for advanced prostate cancer. BMC Cancer 10, 556 (2010).
40. Dai, J. et al. Cabozantinib (XL184) inhibits prostate tumor growth and bone lesion development. Cancer Res. 72, a2851 (2012).
41. Smith, D. C. et al. Cabozantinib in patients with advanced prostate cancer: results of a phase II randomised discontinuation trial. J. Clin. Oncol. 31, 412-419 (2013).
42. Peraldo-Neia, C. et al. Epidermal growth factor receptor (EGFR) mutation analysis, gene expression profiling and EGFR protein expression in primary prostate cancer. BMC Cancer 11, 31 (2011).
43. Jathal, M. K., Chen, L., Mudryj, M. & Ghosh, P. M. Targeting ErbB3: the new RTK(id) on the prostate cancer block. Immunol. Endocr. Metab. Agents Med. Chem. 11, 131-149 (2011).
44. Gupta, P. et al. Development of an EGFRvIII specific recombinant antibody. BMC Biotechnol. 10, 72 (2010).
45. Li, G. & Wong, A. J. EGF receptor variant III as a target antigen for tumor immunotherapy. Expert Rev. Vaccines 7, 977-985 (2008).
46. Baek, K. H. et al. Correlation of AR, EGFR, and HER2 expression levels in prostate cancer: immunohistochemical analysis and chromogenic in situ hybridization. Cancer Res. Treat. 44, 50-56 (2012).
47. Weber, D. C. et al. The prognostic value of expression of HIF1alpha, EGFR and VEGF-A, in localized prostate cancer for intermediate-and high-risk patients treated with radiation therapy with or without androgen deprivation therapy. Radiat. Oncol. 7, 66 (2012).
48. Fleming, M. T. et al. Association of rash with outcomes in a randomized phase II trial evaluating cetuximab in combination with mitoxantrone plus prednisone after docetaxel for metastatic castration-resistant prostate cancer. Clin. Genitourin. Cancer 10, 6-14 (2012).
49. Pezaro, C. et al. An open-label, single-arm phase two trial of gefitinib in patients with advanced or metastatic castration-resistant prostate cancer. Am. J. Clin. Oncol. 32, 338-341 (2009).
50. Carrion-Salip, D. et al. Androgen-independent prostate cancer cells circumvent EGFR inhibition by overexpression of alternative HER receptors and ligands. Int. J. Oncol. 41, 1128-1138 (2012).
51. Ziada, A. et al. The use of trastuzumab in the treatment of hormone refractory prostate cancer; phase II trial. Prostate 60, 332-337 (2004).
52. Liu, G. et al. Eastern Cooperative Oncology Group Phase II Trial of lapatinib in men with biochemically relapsed, androgen dependent prostate cancer. Urol. Oncol. 31, 211-218 (2011).
53. Karapetis, C. S. et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N. Engl. J. Med. 359, 1757-1765 (2008).
54. Coulson-Thomas, V. J. et al. Fibroblast and prostate tumor cell cross-talk: fibroblast differentiation, TGF-beta, and extracellular matrix down-regulation. Exp. Cell. Res. 316, 3207-3226 (2010).
55. Franco, O. E. et al. Altered TGF-beta signaling in a subpopulation of human stromal cells promotes prostatic carcinogenesis. Cancer Res. 71, 1272-1281 (2011).
56. Li, X. et al. Prostate tumor progression is mediated by a paracrine TGF-beta/Wnt3a signaling axis. Oncogene 27, 7118-7130 (2008).
57. Li, X. et al. Loss of TGF-beta responsiveness in prostate stromal cells alters chemokine levels and facilitates the development of mixed osteoblastic/osteolytic bone lesions. Mol. Cancer Res. 10, 494-503 (2012).
58. Burgio, S. L. et al. Perspectives on mTOR inhibitors for castration-refractory prostate cancer. Curr. Cancer Drug Targets 12, 940-949 (2012).
59. Yoshimoto, M. et al. PTEN losses exhibit heterogeneity in multifocal prostatic adenocarcinoma and are associated with higher Gleason grade. Mod. Pathol. 26, 435-447 (2012).
60. Wang, J. et al. B-Raf activation cooperates with PTEN loss to drive c-Myc expression in advanced prostate cancer. Cancer Res. 72, 4765-4776 (2012).
61. Agell, L. et al. PI3K signaling pathway is activated by PIK3CA mRNA overexpression and copy gain in prostate tumors, but PIK3CA, BRAF, KRAS and AKT1 mutations are infrequent events. Mod. Pathol. 24, 443-452 (2011).
62. Tsaur, I. et al. Resistance to the mTOR-inhibitor RAD001 elevates integrin alpha2- and beta1-triggered motility, migration and invasion of prostate cancer cells. Br. J. Cancer 107, 847-855 (2012).
63. Nakabayashi, M. et al. Phase II trial of RAD001 and bicalutamide for castration-resistant prostate cancer. BJU Int. 110, 1729-1735 (2012).
64. Mimeault, M., Johansson, S. L. & Batra, S. K. Pathobiological implications of the expression of EGFR, pAkt, NF-kappaB and MIC-1 in prostate cancer stem cells and their progenies. PLoS ONE 7, e31919 (2012).
65. Molina, A. M. et al. Phase 1 trial of everolimus plus sunitinib in patients with metastatic renal cell carcinoma. Cancer 118, 1868-1876 (2012).
66. Rozengurt, E., Sinnett-Smith, J. & Kisfalvi, K. Crosstalk between insulin/insulin-like growth factor-1 receptors and G protein-coupled receptor signaling systems: a novel target for the antidiabetic drug metformin in pancreatic cancer. Clin. Cancer Res. 16, 2505-2511 (2010).
67. Yu, S. et al. Altered prostate epithelial development and IGF-1 signal in mice lacking the androgen receptor in stromal smooth muscle cells. Prostate 71, 517-524 (2011).
68. Beltran, H. et al. Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov. 1, 487-495 (2011).
69. Efstathiou, E. et al. Effects of abiraterone acetate on androgen signaling in castrate-resistant prostate cancer in bone. J. Clin. Oncol. 30, 637-643 (2012).
70. Vander Griend, D. J. et al. Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells. Prostate 70, 90-99 (2010).
71. Niu, Y. N. & Xia, S. J. Stroma-epithelium crosstalk in prostate cancer. Asian J. Androl. 11, 28-35 (2009).
72. Weinstein, I. B. & Joe, A. Oncogene addiction. Cancer Res. 68, 3077-3080 (2008).
73. Jin, J. K., Dayyani, F. & Gallick, G. E. Steps in prostate cancer progression that lead to bone metastasis. Int. J. Cancer 128, 2545-2561 (2011).
74. Mundy, G. R. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat. Rev. Cancer 2, 584-593 (2002).
75. Roodman, G. D. Mechanisms of bone metastasis. Discov. Med. 4, 144-148 (2004).
76. Josson, S., Matsuoka, Y., Chung, L. W., Zhau, H. E. & Wang, R. Tumor-stroma co-evolution in prostate cancer progression and metastasis. Semin. Cell. Dev. Biol. 21, 26-32 (2010).
77. Nannuru, K. C. & Singh, R. K. Tumor-stromal interactions in bone metastasis. Curr. Osteoporos. Rep. 8, 105-113 (2010).
78. Ibrahim, T. et al. Pathogenesis of osteoblastic bone metastases from prostate cancer. Cancer 116, 1406-1418 (2010).
79. Garin-Chesa, P., Old, L. J. & Rettig, W. J. Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc. Natl Acad. Sci. USA 87, 7235-7239 (1990).
80. Tuxhorn, J. A., Ayala, G. E. & Rowley, D. R. Reactive stroma in prostate cancer progression. J. Urol. 166, 2472-2483 (2001).
81. Scott, A. M. et al. A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer. Clin. Cancer Res. 9, 1639-1647 (2003).
82. LeBeau, A. M., Brennen, W. N., Aggarwal, S. & Denmeade, S. R. Targeting the cancer stroma with a fibroblast activation protein-activated promelittin protoxin. Mol. Cancer Ther. 8, 1378-1386 (2009).
83. Brennen, W. N., Rosen, D. M., Wang, H., Isaacs, J. T. & Denmeade, S. R. Targeting carcinoma-associated fibroblasts within the tumor stroma with a fibroblast activation protein-activated prodrug. J. Natl Cancer Inst. 104, 1320-1334 (2012).
84. Orr, B. et al. Reduction of pro-tumorigenic activity of human prostate cancer-associated fibroblasts using Dlk1 or SCUBE1. Dis. Model Mech. 6, 530-536 (2013).
85. Saad, F. et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J. Natl Cancer Inst. 94, 1458-1468 (2002).
86. Saad, F. et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J. Natl Cancer Inst. 96, 879-882 (2004).
87. Ferreira, S., Dormehl, I. & Botelho, M. F. Radiopharmaceuticals for bone metastasis therapy and beyond: a voyage from the past to the present and a look to the future. Cancer Biother. Radiopharm. 27, 535-551 (2012).
88. Parker, C. et al. Overall survival benefit and safety profile of radium-223 chloride, a first-in-class alpha-pharmaceutical: results from a phase III randomized trial (ALSYMPCA) in patients with castration-resistant prostate cancer (CRPC) with bone metastases. J. Clin. Oncol. 30, a8 (2012).
89. Chun, J. Y. et al. Interleukin-6 regulates androgen synthesis in prostate cancer cells. Clin. Cancer Res. 15, 4815-4822 (2009).
90. Azevedo, A., Cunha, V., Teixeira, A. L. & Medeiros, R. IL-6/IL-6R as a potential key signaling pathway in prostate cancer development. World J. Clin. Oncol. 2, 384-396 (2011).
91. Seaton, A. et al. Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation. Carcinogenesis 29, 1148-1156 (2008).
92. Lee, S. O. et al. Interleukin-4 activates androgen receptor through CBP/p300. Prostate 69, 126-132 (2009).
93. Araki, S. et al. Interleukin-8 is a molecular determinant of androgen independence and progression in prostate cancer. Cancer Res. 67, 6854-6862 (2007).
94. Lehrer, S., Diamond, E. J., Mamkine, B., Stone, N. N. & Stock, R. G. Serum interleukin-8 is elevated in men with prostate cancer and bone metastases. Technol. Cancer Res. Treat. 3, 411 (2004).
95. Wise, G. J., Marella, V. K., Talluri, G. & Shirazian, D. Cytokine variations in patients with hormone treated prostate cancer. J. Urol. 164, 722-725 (2000).
96. Royuela, M. et al. Immunohistochemical analysis of the IL-6 family of cytokines and their receptors in benign, hyperplasic, and malignant human prostate. J. Pathol. 202, 41-49 (2004).
97. Karkera, J. et al. The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study. Prostate 71, 1455-1465 (2011).
98. Fizazi, K. et al. Randomised phase II study of siltuximab (CNTO 328), an anti-IL-6 monoclonal antibody, in combination with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer. Eur. J. Cancer 48, 85-93 (2012).
99. US National Library of Medicine. ClinicalTrials.gov [online], http://clinicaltrials.gov/ct2/show/NCT00861614 (2013).
100. US National Library of Medicine. ClinicalTrials.gov [online], http://clinicaltrials.gov/ct2/show/NCT01057810 (2013).
101. Topalian, S. L. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443-2454 (2012).
102. Dulos, J. et al. PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer. J. Immunother. 35, 169-178 (2012).
103. Lin, T. L. & Matsui, W. Hedgehog pathway as a drug target: smoothened inhibitors in development. Onco. Targets Ther. 5, 47-58 (2012).
104. Singh, S. et al. Chemoresistance in prostate cancer cells is regulated by miRNAs and Hedgehog pathway. PLoS ONE 7, e40021 (2012).
105. Karhadkar, S. S. et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 431, 707-712 (2004).
106. Fan, L. et al. Hedgehog signaling promotes prostate xenograft tumor growth. Endocrinology 145, 3961-3970 (2004).
107. Yauch, R. L. et al. A paracrine requirement for hedgehog signalling in cancer. Nature 455, 406-410 (2008).
108. Efstathiou, E. et al. Integrated Hedgehog signaling is induced following castration in human and murine prostate cancers. Prostate 153-161 (2012).
109. Rosen, J. M. & Jordan, C. T. The increasing complexity of the cancer stem cell paradigm. Science 324, 1670-1673 (2009).
110. Frame, F. M. & Maitland, N. J. Cancer stem cells, models of study and implications of therapy resistance mechanisms. Adv. Exp. Med. Biol. 720, 105-118 (2011).
111. Maitland, N. J., Frame, F. M., Polson, E. S., Lewis, J. L. & Collins, A. T. Prostate cancer stem cells: do they have a basal or luminal phenotype? Horm. Cancer 2, 47-61 (2011).
112. Goldstein, A. S., Huang, J., Guo, C., Garraway, I. P. & Witte, O. N. Identification of a cell of origin for human prostate cancer. Science 329, 568-571 (2010).
113. Anaka, M. et al. Stem cell media culture of melanoma results in the induction of a nonrepresentative neural expression profile. Stem Cells 30, 336-343 (2012).
114. Nauseef, J. T. & Henry, M. D. Epithelial-to-mesenchymal transition in prostate cancer: paradigm or puzzle? Nat. Rev. Urol. 8, 428-439 (2011).
115. Sun, Y. et al. Androgen deprivation causes epithelial-mesenchymal transition in the prostate: implications for androgen-deprivation therapy. Cancer Res. 72, 527-536 (2012).
116. Zoubeidi, A. & Gleave, M. Small heat shock proteins in cancer therapy and prognosis. Int. J. Biochem. Cell. Biol. 44, 1646-1656 (2012).
117. Shiota, M. et al. Clusterin mediates TGF-beta-induced epithelial-mesenchymal transition and metastasis via Twist1 in prostate cancer cells. Cancer Res. 72, 5261-5272 (2012).
118. Saramaki, O. R. et al. TMPRSS2: ERG fusion identifies a subgroup of prostate cancers with a favorable prognosis. Clin. Cancer Res. 14, 3395-3400 (2008).
119. Becker-Santos, D. D. et al. Integrin-linked kinase as a target for ERG-mediated invasive properties in prostate cancer models. Carcinogenesis 33, 2558-2567 (2012).
120. Danila, D. C., Pantel, K., Fleisher, M. & Scher, H. I. Circulating tumors cells as biomarkers: progress toward biomarker qualification. Cancer J. 17, 438-450 (2011).
121. de Bono, J. S. et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin. Cancer Res. 14, 6302-6309 (2008).
122. Magbanua, M. J. et al. Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer. BMC Cancer 12, 78 (2012).
123. Miyamoto, D. T. et al. Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer. Cancer Discov. 2, 995-1003 (2012).
124. Shaw, G. et al. Hedgehog signalling in androgen independent prostate cancer. Eur. Urol. 54, 1333-1343 (2008).
125. Figel, S. & Gelman, I. H. Focal adhesion kinase controls prostate cancer progression via intrinsic kinase and scaffolding functions. Anticancer Agents Med. Chem. 11, 607-616 (2011).
126. Eisenhauer, E. A. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228-247 (2009).
127. Scher, H. I. et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J. Clin. Oncol. 26, 1148-1159 (2008).
128. Nievergall, E., Lackmann, M. & Janes, P. W. Eph-dependent cell-cell adhesion and segregation in development and cancer. Cell. Mol. Life Sci. 69, 1813-1842 (2012).
129. Kandouz, M. The Eph/Ephrin family in cancer metastasis: communication at the service of invasion. Cancer Metastasis Rev. 31, 353-373 (2012).
130. Rutkowski, R., Mertens-Walker, I., Lisle, J. E., Herington, A. C. & Stephenson, S. A. Evidence for a dual function of EphB4 as tumor promoter and suppressor regulated by the absence or presence of the ephrin-B2 ligand. Int. J. Cancer 131, E614-E624 (2012).
131. Wang, B. Cancer cells exploit the Eph-ephrin system to promote invasion and metastasis: tales of unwitting partners. Sci. Signal 4, pe28 (2011).
132. Petty, A. et al. A small molecule agonist of EphA2 receptor tyrosine kinase inhibits tumor cell migration in vitro and prostate cancer metastasis in vivo. PLoS ONE 7, e42120 (2012).
133. Vearing, C. et al. Concurrent binding of anti-EphA3 antibody and ephrin-A5 amplifies EphA3 signaling and downstream responses: potential as EphA3-specific tumor-targeting reagents. Cancer Res. 65, 6745-6754 (2005).
134. Araujo, J. C. et al. Dasatinib combined with docetaxel for castration-resistant prostate cancer: results from a phase 1-2 study. Cancer 118, 63-71 (2012).
135. US National Library of Medicine. ClinicalTrials.gov [online], http://clinicaltrials.gov/ct2/show/NCT01685125 (2013).
136. Araujo, J. C. et al. Overall survival (OS) and safety of dasatinib/docetaxel versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC): results from the randomized phase III READY trial. J. Clin. Oncol. 31 (Suppl. 6), aLBA8 (2013).