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Opportunities for Targeted Molecular Therapy for Prostate Cancer

  • Chapter
Management of Prostate Cancer

Part of the book series: Current Clinical Urology ((CCU))

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Abstract

Because of increased screening in the United States, prostate cancer is now frequently diagnosed at a clinically localized stage that is amenable to local therapy. Nevertheless, prostate cancer remains the second most common cause of cancer death in men. A substantial subset of patients with clinically localized prostate cancer will relapse after local therapy, and up to 20% of all patients still present initially with metastatic disease. These patients will generally respond to androgen deprivation therapy, but the vast majority will eventually develop disease progression, refractory to sustained hormonal manipulation. Typically, such patients progress first with a rise in their serum prostate-specific antigen (PSA) level, followed months later by systemic symptoms such as weight loss, fatigue, and complications from metastases, such as bone pain, cord compression, and/or urinary obstruction. Unfortunately, standard therapeutic options at this stage of disease are limited. Although activity has recently been demonstrated with chemotherapy for hormone-refractory prostate cancer (HRPC) patients, the response is generally short-lived (1).

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References

  1. Oh WK, Kantoff PW. Management of hormone refractory prostate cancer: current standards and future prospects. J Urol 1998; 160: 1220–1229.

    PubMed  CAS  Google Scholar 

  2. Isaacs JT. The biology of hormone refractory prostate cancer. Why does it develop? Urol Clin North Am 1999; 26: 263–273.

    PubMed  CAS  Google Scholar 

  3. Linja MJ, Savinainen KJ, Saramaki OR. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res 2001; 61: 3550–3555.

    PubMed  CAS  Google Scholar 

  4. Culig Z, Hobisch A, Cronauer MV, et al. Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-1, keratinocyte growth factor, and epidermal growth factor. Cancer Res 1994; 54: 5474–5478.

    PubMed  CAS  Google Scholar 

  5. Nazareth LV, Weigel NL. Activation of the human androgen receptor through a protein kinase A sinaling pathway. J Biol Chem 1996; 271: 19900–19907.

    PubMed  CAS  Google Scholar 

  6. Sadar MD. Androgen-independent induction of prostate-specific antigen gene expression via crosstalk between the androgen receptor and protein kinase A signal transduction pathways. J Biol Chem 1999; 274: 7777–7783.

    PubMed  CAS  Google Scholar 

  7. Craft NA, Shostak Y, Carey M, Sawyers CL. A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the Her-2/neu tyrosine kinase. Nature Med 1999; 5: 280–285.

    PubMed  CAS  Google Scholar 

  8. Putz T, Culig Z, Eder IE, et al. Epidermal growth factor (EGF) receptor blockade inhibits the action of EGF, insulin-like growth factor 1, and a protein kinase A activator on the mitogen-activated protein kinase pathway in prostate cancer cell lines. Cancer Res 1999; 1999: 227–233.

    Google Scholar 

  9. Yeh S, Lin H-K, Kang H-Y, et al. From Her2/Neu signal cascade to androgen receptor and its co-activators: a novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells. Proc Natl Acad Sci USA 1999; 96: 5458–5463.

    PubMed  CAS  Google Scholar 

  10. Lou W, Ni Z, Dyer K, et al. Interleukin-6 induces prostate cancer cell growth accompanied by activation of stat3 signaling pathway. Prostate 2000; 42: 239–242.

    PubMed  CAS  Google Scholar 

  11. Trump DL, Smith DC, Stiff D, et al. A phase II trial of all-trans retinoic acid in hormone-refractory prostate cancer: a clinical trial with detailed pharmacokinetic analysis. Cancer Chemother Pharmacol 1997; 39: 349–356.

    PubMed  CAS  Google Scholar 

  12. De Vos S, Holden S, Heber D, et al. Effects of potent vitamin D3 analogs on clonal proliferation of human prostate cell lines. Prostate 1997; 31: 77–83.

    PubMed  Google Scholar 

  13. Schwartz GG, Wang MH, Zang M, et al. 1-alpha,25-dihydroxyvitamin D (calcitriol) inhibits the invasiveness of human prostate cancer cells. Cancer Epidemiol Biomarkers Prev 1997; 6: 727–732.

    PubMed  CAS  Google Scholar 

  14. Kubota T, Koshizuka K, Williamson EA, et al. Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res 1998; 58: 3344–3352.

    PubMed  CAS  Google Scholar 

  15. Schwartz GG, Hulka BS. Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res 1990; 10: 1307–1311.

    PubMed  CAS  Google Scholar 

  16. Corder EH, Guess HA, Hulka BS, et al. Vitamin D and prostate cancer: a prediagnostic study with stored sera. Cancer Epidemiol Biomarkers Prev 1993; 2: 467–472.

    PubMed  CAS  Google Scholar 

  17. Miller GJ, Stapleton GE, Ferrara JA, et al. The human prostatic carcinoma cell line LNCaP expresses biologically active, specific receptors for 1,25-dihydroxyvitamin D3. Cancer Res 1992; 52: 515–520.

    PubMed  CAS  Google Scholar 

  18. Skowronski RJ, Peehl DM, Feldman D. Vitamin D and prostate cancer: 1,25-dihydroxyvitamin D3 receptors and actions in human prostate cancer cell lines. Endocrinology 1993; 132: 1952–1960.

    PubMed  CAS  Google Scholar 

  19. Peehl DM, Skowronski RJ, Leung GK, et al. Antiproliferative effects of 1,25-dihydroxyvitamin D3 on primary cultures of human prostatic cells. Cancer Res 1994; 54: 805–810.

    PubMed  CAS  Google Scholar 

  20. Baker AR, McDonnell DP, Hughes M, et al. Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci USA 1988; 85: 3294–3298.

    PubMed  CAS  Google Scholar 

  21. Evans RM. The steroid and thyroid hormone receptor superfamily. Science 1988; 240: 889–895.

    PubMed  CAS  Google Scholar 

  22. Haussler MR, Whitfield GK, Haussler CA, et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Min Res 1998; 13: 325–349.

    CAS  Google Scholar 

  23. Freedman LP. Transcriptional targets of the vitamin D3 receptor mediated cell cycle arrest and differentiation. J Nutr 1999; 129: 581S–586S.

    PubMed  CAS  Google Scholar 

  24. Getzenberg RH, Light BW, Lapco PE, et al. Vitamin D inhibition of prostate adenocarcinoma growth and metastasis in the Dunning rat prostate model system. Urology 1997; 50: 999–1006.

    PubMed  CAS  Google Scholar 

  25. Modzelewski RA, Hershberger PA, Johnson CS, Trump DL. Apoptotic effects of paclitaxel and calcitriol in rat dunning MLL and human PC-3 prostate tumor cells in vitro. Proc Am Assoc Cancer Res 1999; 40: 580a.

    Google Scholar 

  26. Osborn JL, Schwartz GG, Smith DC, et al. Phase II trial of oral 1,25-dihydroxyvitamin D (calcitriol) in hormone refractory prostate cancer. Urol Oncol 1995; 1: 195–198.

    PubMed  CAS  Google Scholar 

  27. Smith DC, Johnson CS, Freeman CC, et al. A phase I trial of subcutaneous calcitriol (1,25-dihydroxycholecalciferol) in patients with advanced malignancy. Clin Cancer Res 1999; 5: 1339–1345.

    PubMed  CAS  Google Scholar 

  28. Beer TM, Munar M, Henner WD. A phase I trial of pulse calcitriol in patients with refractory malignancies. Cancer 2001; 91: 2431–2439.

    PubMed  CAS  Google Scholar 

  29. Gross C, Stamey T, Hancock S, Feldman D. Treatment of early recurrent prostate cancer with 1,25- dihydroxyvitamin D3 (calcitriol). J Urol 1998; 159: 2035–2040.

    PubMed  CAS  Google Scholar 

  30. Beer TM, Eilers KM, Garzotto M, et al. Weekly high-dose calcitrol and docetaxel in metastatic androgen-independent prostate cancer. J Clin Oncol 2003; 21: 123–128.

    PubMed  CAS  Google Scholar 

  31. Trump DL, Serafine S, Brufsky A, et al. High dose calcitriol (1,25(OH)2 vitamin D3) + dexamethasone in androgen independent prostate cancer (AIPC). Proc Am Soc Clin Oncol 2000; 19: 337a.

    Google Scholar 

  32. Johnson CS, Egorin MJ, Zuhowski R, et al. Effects of high dose calcitriol (1,25-dihydroxyvitamin D3 on the pharmacokinetics of paclitaxel or carboplatin: results of two phase I studies. Proc Am Soc Clin Oncol 2000; 19: 210a.

    Google Scholar 

  33. Schwartz GG, Hill CC, Oeler TA, et al. 1,24-Dihydroxy-16-ene-23-yne-vitamin D and prostate cancer cell proliferation in vivo. Urology 1995; 46: 365–369.

    PubMed  CAS  Google Scholar 

  34. Campbell MJ, Reddy GS, Koeffler HP. Vitamin D3 analogs and their 24-oxo metabolites equally inhibit clonal proliferation of a variety of cancer cells but have differing molecular effects. J Cell Biochem 1997; 66: 413–425.

    PubMed  CAS  Google Scholar 

  35. Hansen CM, Maenpaa PH. EB 1089, a novel vitamin D analog with strong antiproliferative and differentiation inducing effects on target cells. Biochem Pharmacol 1997; 54: 1173–1179.

    PubMed  CAS  Google Scholar 

  36. Gulliford T, English J, Colston KW, et al. A phase I study of vitamin D analogue EB 1089 in patients with advanced breast and colorectal cancer. Br J Cancer 1998; 78: 6–13.

    PubMed  CAS  Google Scholar 

  37. Chawla A, Schwarz EJ, Dimaculangan DD, Lazar MA. Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 1994; 135: 798–800.

    PubMed  CAS  Google Scholar 

  38. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR-gamma-2, a lipid-activated transcription factor. Cell 1994; 79: 1147–1156.

    PubMed  CAS  Google Scholar 

  39. Kliewer SA, Forman BM, Blumberg B, et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA 1994; 91: 7355–7359.

    PubMed  CAS  Google Scholar 

  40. Yu K, Bayona W, Kallen W, et al. Differential activation of the peroxisome proliferator-activated receptors by eicosanoids. J Biol Chem 1995;270:23975–23983.

    Google Scholar 

  41. Mueller E, Smith M, Sarraf P, et al. Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer. Proc Natl Acad Sci USA 2000; 97: 10990–10995.

    PubMed  CAS  Google Scholar 

  42. Butler R, Mitchell SH, Tindall DJ, Young CY. Nonapoptotic cell death associated with S-phase arrest of prostate cancer cells via the peroxisome proliferator-activated receptor gamma ligand, 15-deoxydelta-12,14-prostaglandin J2. Cell Growth Differ 2000; 11: 49–61.

    PubMed  CAS  Google Scholar 

  43. Segawa Y, Yoshimura R, Hase T, et al. Expression of peroxisome proliferator-activated receptor (PPAR) in human prostate cancer. Prostate 2002; 51: 108–116.

    PubMed  CAS  Google Scholar 

  44. Shappell SB, Gupta RA, Manning S, et al. 15S- Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor gamma and inhibits proliferation in PC-3 prostate carcinoma cells. Cancer Res 2001; 61: 497–503.

    PubMed  CAS  Google Scholar 

  45. Hisatake J, Ikezoe T, Carey M, et al. Down-regulation of prostate-specific antigen expression by ligands for peroxisome proliferator-activated receptor gamma in human prostate cancer. Cancer Res 2000; 60: 5494–5498.

    PubMed  CAS  Google Scholar 

  46. Peehl DM, Wong S, Bazinet M, Stamey TA. In vitro studies of human prostate epithelial cells. Attempts to identify distinguishing features of malignant cells. Growth Factors 1989; 1: 237–250.

    Google Scholar 

  47. Elson SD, Browne CA, Thorburn GD. Identification of epidermal growth factor-like activity in human male reproductive tissue and fluids. J Clin Endocrinol Metab 1984; 58: 589–595.

    PubMed  CAS  Google Scholar 

  48. Gregory J, Willshire IR, Kavanagh JP, et al. Urogastrone-epidermal growth factor concentration in prostatic fluid of normal individuals and patients with benign prostatic hypertrophy. Clin Sci 1986; 70: 359–363.

    PubMed  CAS  Google Scholar 

  49. Fowler JE, Lau JLY, Ghosh L, et al. Epidermal growth factor and prostatic carcinoma: an immunohistochemical study. J Urol 1988; 139: 857–861.

    PubMed  Google Scholar 

  50. Maddy SQ, Chisholm GD, Hawkins RA, et al. Localization of epidermal growth factor receptors in the human prostate by biochemical and immunocytochemical methods. J Endocrinol 1987; 113: 147–153.

    PubMed  CAS  Google Scholar 

  51. Schuurmans ALG, Bolt J, Mulder E. Androgens stimulate both growth rate and epidermal growth factor receptor activity of the human prostate tumor cell LNCaP. Prostate 1988; 12: 55–63.

    PubMed  CAS  Google Scholar 

  52. Chung LW, Li W, Gleave ME, et al. Human prostate cancer model: roles of growth factors and extra-cellular matrices. J Cell Biochem Suppl 1992; 16: 99–105.

    Google Scholar 

  53. De Miguel P, Royuela Bethencourt R, et al. Immunohistochemical comparative analysis of transforming growth factor alpha, epidermal growth factor, and epidermal growth factor receptor in normal, hyperplastic and neoplastic human prostates. Cytokine 1999; 11: 722–727.

    PubMed  Google Scholar 

  54. Robertson CN, Roberson KM, Herzberg AJ, et al. Differential immunoreactivity of transforming growth factor alpha in benign, dysplastic and malignant prostatic tissue. Surg Oncol 1994; 3: 237–242.

    PubMed  CAS  Google Scholar 

  55. MacDonald A, Habib FK. Divergent responses to epidermal growth factor in hormone sensitive and insensitive human prostate cancer cell lines. Br J Cancer 1992; 65: 177–182.

    PubMed  CAS  Google Scholar 

  56. Di Lorenzo G, Tortora G, D’Armiento FP, et al. Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer. Clin Cancer Res 2002; 8: 3438–3444.

    PubMed  Google Scholar 

  57. Olapade-Olaopa EO, Moscatello DK, MacKay EH, et al. Evidence for the differential expression of a variant EGF receptor protein in human prostate cancer. Br J Cancer 2000; 82: 186–194.

    PubMed  CAS  Google Scholar 

  58. Jarrad DF, Blitz BF, Smith RC, et al. Effects of the epidermal growth factor receptor in human prostatic tissue. J Urol 1994; 152: 2120–2124.

    Google Scholar 

  59. Turner T, Chen P, Goodly LJ, Wells A. EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate carcinoma cells. Clin Exp Metastasis 1996; 14: 409–418.

    PubMed  CAS  Google Scholar 

  60. Kassis J, Moellinger J, Lo H, et al. A role for phospholipase C-gamma-mediated signaling in tumor cell invasion. Clin Cancer Res 1999; 5: 2251–2260.

    PubMed  CAS  Google Scholar 

  61. Ciardiello F, Caputo R, Bianco R, et al. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res 2000; 6: 2053–2063.

    PubMed  CAS  Google Scholar 

  62. Sgambato A, Ardito R, Cangiano R. Targeted inhibition of the epidermal growth factor receptor tyrosine kinase (EGFR-TK) by ZD1839 (‘Iressa’) induces cell-cycle arrest and inhibits proliferation in prostate cancer cells. Proc Am Assoc Cancer Res 2002; 43: 3887a.

    Google Scholar 

  63. Sirotnak FM, Zakowski MF, Miller VA, et al. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD 1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin Cancer Res 2000; 6: 4885–4892.

    PubMed  CAS  Google Scholar 

  64. Geller JA, Galkin AV, Mullen L, et al. Effects of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) ZD1839 (‘Iressa’) on androgen-dependent and androgen-independent human prostate tumor xenografts: growth inhibition and characteristics of resistant tumors. Proc Am Assoc Cancer Res 2002; 43: 4971a.

    Google Scholar 

  65. Barton J, Blackledge G, Wakeling A. Growth factors and their receptors: new targets for prostate cancer therapy. Urology 2001; 58: 114–122.

    PubMed  CAS  Google Scholar 

  66. Trump D, Wilding G, Small E, et al. A pilot trial of ZD1839 (‘Iressa’), an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in combination with docetaxel and estramustine in patients with hormone refractory prostate cancer (HRPC). Presented at the Annual Meeting of the American Urological Association, Orlando, FL, 2002.

    Google Scholar 

  67. Goldstein NI, Prewett M, Zuklys K, et al. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res 1995; 1: 1311–1318.

    PubMed  CAS  Google Scholar 

  68. Slovin SF, Livingston PO, Rosen N, et al. Targeted therapy for prostate cancer: the MSKCC approach. Semin Oncol 1996; 23: 41–48.

    PubMed  CAS  Google Scholar 

  69. Baselga J, Pfister MR, Cooper R, et al. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol 2000; 18: 904–914.

    PubMed  CAS  Google Scholar 

  70. Slovin SF, Kelly WK, Cohen R, et al. Epidermal growth factor receptor (EGFr) monoclonal antibody (MoAb) C225 and doxorubicin (DOC) in androgen independent (AI) prostate cancer (PC): results of a phase Ib/II study [abstract]. Proc Am Soc Clin Oncol 1997; 16: 1108a.

    Google Scholar 

  71. Yang X, Jia X, Corvalan JRF, et al. Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without chemotherapy. Cancer Res 1999; 59: 1236–1243.

    PubMed  CAS  Google Scholar 

  72. Yang X, Wang P, Fredlin P, Davis CG. ABX-EGF, a fully human anti-EGF receptor monoclonal antibody: inhibition of prostate cancer in vitro and in vivo. Proc Am Soc Clin Oncol 2002; 21: 2454a.

    Google Scholar 

  73. Coussens L, Yang-Feng TL, Liao YC, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985; 230: 1132–1139.

    PubMed  CAS  Google Scholar 

  74. Klapper L, Glathe S, Vaisman N, et al. The erbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared co-receptor for multiple stroma-derived growth factors. Proc Natl Acad Sci USA 1999; 96: 4995–5000.

    PubMed  CAS  Google Scholar 

  75. Mellon JK, Thompson S, Charlton RG, et al. p53, c-erbB-2 and the epidermal growth factor receptor in benign and malignant prostate. J Urol 1992; 147: 495–499.

    Google Scholar 

  76. Kuhn EJ, Kurnot RA, Sesterhenn IA. Expression of the c-erb-B-2(HER-2/neu) oncoprotein in human prostatic carcinoma. J Urol 1993; 150: 1427–1433.

    PubMed  CAS  Google Scholar 

  77. Ross JS, Sheehan CM, Hayner-Buchan AM, et al. HER-2/neu gene amplification status in prostate cancer by fluorescence in situ hybridization. Hum Pathol 1997; 28: 827–833.

    PubMed  CAS  Google Scholar 

  78. Kallakury BV, Sheehan CE, Ambros RA, et al. Correlation of p34cdc2 cyclin-dependent kinase over-expression, CD44s downregulation, and HER-2/neu oncogene amplification with recurrence in pro-static adenocarcinomas. J Clin Oncol 1998; 16: 1302–1309.

    PubMed  CAS  Google Scholar 

  79. Mark HF, Feldman D, Das S, et al. Fluorescence in situ hybridization study of HER-2/neu oncogene amplification in prostate cancer. Exp Mol Pathol 1999; 66: 170–178.

    PubMed  CAS  Google Scholar 

  80. Shi Y, Brands FH, Chatterjee S, et al. Her-2/neu expression in prostate cancer: high level of expression associated with exposure to hormone therapy and androgen independent disease. J Urol 2001; 166: 1514–1519.

    PubMed  CAS  Google Scholar 

  81. Signoretti S, Montironi R, Manola J, et al. Her-2-neu expression and progression toward androgen independence in human prostate cancer. J Natl Cancer Inst 2000; 92: 1918–1925.

    PubMed  CAS  Google Scholar 

  82. Carter P, Presta L, Gorman CM, et al. Humanization of an anti-p 185HER2 antibody for human cancer treatment. Proc Natl Acad Sci USA 1992; 89: 4285–4289.

    PubMed  CAS  Google Scholar 

  83. Pegram MD, Lipton A, Hayes DF, et al. Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 1998; 16: 2659–2671.

    PubMed  CAS  Google Scholar 

  84. King CR, Kasprzyk PG, Fischer PH, et al. Preclinical testing of an anti-erbB-2 recombinant toxin. Breast Cancer Res Treat 1996; 38: 19–25.

    PubMed  CAS  Google Scholar 

  85. Wennstrom S, Hawkins P, Cooke F, et al. Activation of phosphoinositide 3-kinase is required for PDGF-stimulated membrane ruffling. Curr Biol 1994; 5: 385–393.

    Google Scholar 

  86. Wennstrom S, Siegbahn A, Yokote K, et al. Membrane ruffling and chemotaxis transduced by the PDGF beta-receptor require the binding site for phosphatidylinositol 3′ kinase. Oncogene 1994; 9: 651–660.

    PubMed  CAS  Google Scholar 

  87. Bejeck B, Li D, Deuel TF. Transformation by v-sis occurs by an internal autoactivation mechanism. Science 1989; 245: 1496–1499.

    Google Scholar 

  88. DiMaio D, Lai CC, Klein O. Vivocrine transformation: the intersection between viral transforming proteins and cellular signal transduction pathways. Annu Rev Microbiol 1998; 52: 397–421.

    PubMed  CAS  Google Scholar 

  89. Peehl DM, Sellars RG. Basic FGF, EGF, and PDGF modify TGF-beta induction of smooth muscle cell phenotype in human prostatic stromal cells. Prostate 1998;35:125–134.

    Google Scholar 

  90. Lindahl P, Johansson BR, Leveen P, et al. Pericyte loss and microaneurysm formation in PDGF-B deficient mice. Science 1997; 277: 242–245.

    PubMed  CAS  Google Scholar 

  91. Pietras K, Ostman A, Sjoquist M, et al. Inhibition of platelet derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors. Cancer Res 2001; 61: 2929–2934.

    PubMed  CAS  Google Scholar 

  92. Fudge K, Bostwick DG, Stearns ME. Platelet-derived growth factor A and B chains and the alpha and beta receptors in prostatic intraepithelial neoplasia. Prostate 1996; 29: 282–286.

    PubMed  CAS  Google Scholar 

  93. Fudge K, Wang CY, Stearns ME. Immunohistochemistry analysis of platelet-derived growth factor A and B chains and platelet-derived growth factor alpha and beta receptor expression in benign prostatic hyperplasias and Gleason-graded human prostate adenocarcinomas. Mod Pathol 1994; 7: 549–554.

    PubMed  CAS  Google Scholar 

  94. Chott A, Zijie S, Morganstern D, et al. Tyrosine kinases expressed in vivo by human prostate cancer bone marrow metastases and loss of the type I insulin-like growth factor receptor. Am J Pathol 1999; 155: 1271–1279.

    PubMed  CAS  Google Scholar 

  95. Shawver LK, Schwartz DP, Mann E, et al. Inhibition of platelet-derived growth factor-mediated signal transduction and tumor growth by N-[4-trifluororomethyl)-phenyl]5-methylisoxazole-4-carbamide. Clin Cancer Res 1997; 3: 1167–1177.

    PubMed  CAS  Google Scholar 

  96. Ko Y-J, Small EJ, Kabbinavar F, et al. A multi-institutional phase II study of SU101, a platelet-derived growth factor receptor inhibitor, for patients with hormone-refractory prostate cancer. Clin Cancer Res 2001; 7: 800–805.

    PubMed  CAS  Google Scholar 

  97. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001; 344: 1031–1037.

    PubMed  CAS  Google Scholar 

  98. Buchdunger E, Cioffi CL, Law N, et al. Abl protein-tyrosine kinase inhibitor STI-571 inhibits in vitro signal transduction mediated by c-Kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 2000; 295: 139–145.

    PubMed  CAS  Google Scholar 

  99. Vehara H, Kim SJ, Karashima T, et al. Effects of blocking platelet-derived growth factor receptor signaling in a mouse model of experimental prostate cancer bone metastases. J Natl Cancer Inst 2003; 95: 458–470.

    Google Scholar 

  100. George D. Platelet-derived growth factor receptors: a therapeutic target in solid tumors. Semin Oncol 2001; 28: 27–33.

    PubMed  CAS  Google Scholar 

  101. Peterziel H, Mink S, Schonert A, et al. Rapid signaling by androgen receptor in prostate cancer cells. Oncogene 1999; 18: 6322–6329.

    PubMed  CAS  Google Scholar 

  102. Mansour SJ, Matten WT, Hermann AS, et al. Transformation of mammalian cells by constitutively active MAP kinase kinase. Science 1994; 265: 966–970.

    PubMed  CAS  Google Scholar 

  103. Magi-Galluzzi C, Mishra R, Fiorentino M, et al. Mitogen-activated protein kinase phosphatase 1 is overexpressed in prostate cancers and is inversely related to apoptosis. Lab Invest 1997; 76: 37–51.

    PubMed  CAS  Google Scholar 

  104. Gioeli D, Mandell JW, Petroni GR, et al. Activation of mitogen-activated protein kinase associated with prostate cancer progression. Cancer Res 1999; 59: 279–284.

    PubMed  CAS  Google Scholar 

  105. Sharma Y, Agarwal C, Singh AK, Agarwal R. Inhibitory effect of silibinin on ligand binding to erbB 1 and associated mitogenic signaling, growth, and DNA synthesis in advanced human prostate carcinoma cells. Mol Carcinog 2001; 30: 224–236.

    PubMed  CAS  Google Scholar 

  106. Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997; 275: 1943–1947.

    PubMed  CAS  Google Scholar 

  107. Vlietstra RJ, van Alewijk DC, Hermans KG, et al. Frequent inactivation of PTEN in prostate cancer cell lines and xenografts. Cancer Res 1998; 58: 27–20.

    Google Scholar 

  108. Whang YE, Wu X, Suzuki H, et al. Inactivation of the tumor suppressor PTEN/MMAC 1 in advanced human prostate cancer through loss of expression. Proc Natl Acad Sci USA 1998; 95: 5246–5250.

    PubMed  CAS  Google Scholar 

  109. Stambolic V, Suzuki A, de la Pompa JL, et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 1998; 95: 29–39.

    PubMed  CAS  Google Scholar 

  110. Wu X, Senechal K, Neshat MS, et al. The PTEN/MMAC 1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway. Proc Natl Acad Sci USA 1998; 95: 15587–15591.

    PubMed  CAS  Google Scholar 

  111. Tamura M, Gu J, Danen EH, et al. PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway. J Biol Chem 1999; 274: 20693–20703.

    PubMed  CAS  Google Scholar 

  112. Hagan M, Wang L, Hanley JR, et al. Ionizing radiation-induced mitogen-activated protein (MAP) kinase activation in DU145 prostate carcinoma cells: MAP kinase inhibition enhances radiation-induced cell killing and G2/M arrest. Radiat Res 2000; 153: 371–383.

    PubMed  CAS  Google Scholar 

  113. Ramaswamy S, Nakamura N, Vazquez F, et al. Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/AKT pathway. Proc Natl Acad Sci USA 1999; 96: 2110–2115.

    PubMed  CAS  Google Scholar 

  114. Graff JR, Konicek BW, McNulty AM, et al. Increased AKT activity contributes to prostate cancer progression by dramatically accelerating prostate tumor growth and diminishing p27kip1 expression. J Biol Chem 2000;275:24500–24505.

    Google Scholar 

  115. Nakamura N, Ramaswamy S, Vazquez F, et al. Forkhead transcription factors are critical effectors of cell death and cell cycle arrest downstream of PTEN. Mol Cell Biol 2000; 20: 8969–8982.

    PubMed  CAS  Google Scholar 

  116. Cantley LC, Neel BG. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci USA 1999; 96: 4240–4245.

    PubMed  CAS  Google Scholar 

  117. Nesterov A, Lu X, Johnson M, et al. Elevated AKT activity protects the prostate cancer cell line LNCaP from TRAIL-induced apoptosis. J Biol Chem 2001; 276: 10767–10774.

    PubMed  CAS  Google Scholar 

  118. Carson JP, Kulik G, Weber MJ. Antiapoptotic signaling in LNCaP prostate cancer cells: a survival signaling pathway independent of phosphatidylinositol 3’-kinase and Akt/protein kinase B. Cancer Res 1999; 59: 1449–1453.

    PubMed  CAS  Google Scholar 

  119. Maehama T, Dixon JE. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-triphosphate. J Biol Chem 1998;273:13, 375–13, 378.

    Google Scholar 

  120. Morimoto AM, Tomlinson MG, Nakatani K, et al. The MMAC1 tumor suppressor phosphatase inhibits phospholipase C and integrin-linked kinase activity. Oncogene 2000; 19: 200–209.

    PubMed  CAS  Google Scholar 

  121. Tamura M, Gu J, Matsumoto K, et al. Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 1998; 280: 1614–1617.

    PubMed  CAS  Google Scholar 

  122. Tamura M, Gu J, Takino T, Yamada KM. Tumor suppressor PTEN inhibition of cell invasion, migration, and growth: differential involvement of focal adhesion kinase and p130Cas. Cancer Res 1999; 59: 442–449.

    PubMed  CAS  Google Scholar 

  123. Gu J, Tamura M, Pankov R, et al. Shc and FAK differentially regulate cell motility and directionality modulated by PTEN. J Cell Biol 1999; 146: 389.

    PubMed  CAS  Google Scholar 

  124. Koul D, Shen R, Garyali A, et al. MMAC/PTEN tumor suppressor gene regulates vascular endothelial growth factor-mediated angiogenesis in prostate cancer. Int J Oncol 2002; 21: 469–475.

    PubMed  CAS  Google Scholar 

  125. Zhong H, Chiles K, Feldser D, et al. Modulation of hypoxia-inducible factor 1a expression by the epidermal growth factor phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res 2000; 60: 1541–1545.

    PubMed  CAS  Google Scholar 

  126. Davies MA, Kim SJ, Parikh NU, et al. Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clin Cancer Res 2002; 8: 1904–1914.

    PubMed  CAS  Google Scholar 

  127. Eberhart CE, Coffey RJ, Radhika A, et al. Up-regulation of cyclooxygenase-2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994; 107: 1183–1188.

    PubMed  CAS  Google Scholar 

  128. Sano H, Kawahito Y, Wilder RL, et al. Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 1995; 55: 3785–3789.

    PubMed  CAS  Google Scholar 

  129. DuBois RN, Giardiello FM, Smalley WE. Nonsteroidal anti-inflammatory drugs, eicosanoids and colorectal cancer prevention. Gastroenterol Clin North Am 1996; 25: 773–791.

    PubMed  CAS  Google Scholar 

  130. Kirschenbaum A, Klausner AP, Lee R, et al. Expression of cyclooxygenase-1 and cyclooxygenase-2 in the human prostate. Urology 2000; 56: 671–675.

    PubMed  CAS  Google Scholar 

  131. Yoshimura R, Sano H, Masuda C, et al. Expression of cyclooxygenase-2 in prostate carcinoma. Cancer 2000; 89: 589–596.

    PubMed  CAS  Google Scholar 

  132. Liu X-H,Yao S, Kirschenbaum A, et al. NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells. Cancer Res 1998; 58: 4245–4249.

    PubMed  CAS  Google Scholar 

  133. Liu X-H, Kirschenbaum A, Yao S, et al. Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo. J Urol 2000; 164: 820–825.

    PubMed  CAS  Google Scholar 

  134. Kamijo T, Sato T, Nagatomi Y, Kitamura T. Induction of apoptosis by cyclooxygenase-2 inhibitors in prostate cancer cell lines. Int J Urol 2001; 8: S35–S39.

    PubMed  CAS  Google Scholar 

  135. Hsu A-L, Ching T-T,. Wang D-S, et al. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem 2000;275:11, 397–11, 403.

    Google Scholar 

  136. Song X, Lin H-P, Johnson AJ, et al. Cyclooxygenase-2, player or spectator in cyclooxygenase-2 inhibitor-induced apoptosis in prostate cancer cells. J Natl Cancer Inst 2002; 94: 585–591.

    PubMed  CAS  Google Scholar 

  137. Zhu J, Song X, Lin H-P, et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J Natl Cancer Inst 2002; 94: 1745–1757.

    PubMed  CAS  Google Scholar 

  138. Prescott SM, White RL. Self-promotion? Intimate connections between APC and prostaglandin H synthase-2. Cell 1996; 87: 783–786.

    PubMed  CAS  Google Scholar 

  139. Badawi AF. The role of prostaglandin synthase in prostate cancer. BJU Int 2000; 85: 451–462.

    PubMed  CAS  Google Scholar 

  140. Form DM, Auerbach R. Prostaglandin E2 and angiogenesis. Proc Soc Exp Biol Med 1983; 172: 214–218.

    PubMed  CAS  Google Scholar 

  141. Schmedtje JFJ, Ji YS, Liu WL, et al. Hypoxia induces cyclooxygenase-2 via the NF-kappa-B p65 transcription factor in human vascular endothelial cells. J Biol Chem 1997; 272: 601–608.

    PubMed  CAS  Google Scholar 

  142. Tsujii M, Kawano S, Tsuji S, et al. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998; 93: 705–716.

    PubMed  CAS  Google Scholar 

  143. Fujita H, Kiyoshi K, Keller ET, et al. Cyclooxygenase-2 promotes prostate cancer progression. Prostate 2002; 53: 232–240.

    PubMed  CAS  Google Scholar 

  144. Simonson MS, Herman WH. Protein kinase C and protein tyrosine kinase activity contribute to mitogenic signaling by endothelin-1. Cross-talk between G protein-coupled receptors and pp60c-src. J Biol Chem 1993; 268: 9347–9357.

    PubMed  CAS  Google Scholar 

  145. Hirata Y, Emori T, Eguchi S, et al. Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J Clin Invest 1993; 91: 1367–1373.

    PubMed  CAS  Google Scholar 

  146. Owada A, Tomita K, Terada Y, et al. Endothelin (ET)-3 stimulates cyclic guanosine 3’,5’-monophosphate production via ETB receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells. J Clin Invest 1994; 93: 556–563.

    PubMed  CAS  Google Scholar 

  147. Tsukahara H, Ende H, Magazine H, et al. Molecular and functional characterization of the non-selective ET-B receptor in endothelial cells. J Biol Chem 1994; 269: 21778–21785.

    PubMed  CAS  Google Scholar 

  148. Boulanger C, Luscher TF. Release of endothelin from the porcine aorta: inhibition by endothelinderived nitric oxide. J Clin Invest 1990; 85: 587–590.

    PubMed  CAS  Google Scholar 

  149. Goligorski MS, Tsukahara H, Magazine H, et al. Termination of endothelin signaling: role of nitric oxide. J Cell Physiol 1994; 158: 485–494.

    Google Scholar 

  150. Yohn JJ, Smith C, Stevens T, et al. Autoregulation of endothelin-1 secretion by cultured human keratinocytes via the endothelin B receptor. Biochim Biophys Acta 1994; 1224: 454–458.

    PubMed  Google Scholar 

  151. Fukahiro T, Fujikawa T, Ozaki S, et al. Clearance of circulating endothelin-1 by ET-B receptors in rats. Biochem Biophys Res Commun 1994; 199: 1461–1465.

    Google Scholar 

  152. Nelson JB, Chan-Tack K, Hedican SP, et al. Endothelin-1 production and decreased endothelin-B receptor expression in advanced prostate cancer. Cancer Res 1996; 56: 663–668.

    PubMed  CAS  Google Scholar 

  153. Nelson JB, Lee WH, Nguyen SH, et al. Methylation of the 5’ CpG island of the endothelin B receptor gene is common in human prostate cancer. Cancer Res 1997; 57: 35–37.

    PubMed  CAS  Google Scholar 

  154. Gohji K, Kitazawa S, Tamada H, et al. Expression of endothelin receptor associated with prostate cancer progression. J Urol 2001; 165: 1033–1036.

    PubMed  CAS  Google Scholar 

  155. Nelson JB, Hedican SP, George DJ, et al. Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med 1995; 1: 944–949.

    PubMed  CAS  Google Scholar 

  156. Le Brun G, Aubin P, Soliman H, et al. Upregulation of endothelin 1 and its precursor by IL-1beta, TNF-alpha, and TGF-beta in the PC3 human prostate cancer cell line. Cytokine 1999; 11: 157–162.

    PubMed  Google Scholar 

  157. Granchi S, Brocchi S, Bonaccorsi L, et al. Endothelin-1 production by prostate cancer cell lines is up-regulated by factors involved in cancer progression and down-regulated by androgens. Prostate 2001; 49: 267–277.

    PubMed  CAS  Google Scholar 

  158. Kanse SM, Wijelath E, Kanthou C, et al. The proliferative responsiveness of human vascular smooth muscle cells to endothelin correlates with endothelin receptor density. Lab Invest 1995; 72: 376–382.

    PubMed  CAS  Google Scholar 

  159. Daub H, Weiss FU, Wallasch C. Role of transactivation of the EGF receptor in signaling by G-protein-coupled receptors. Nature 1996; 379: 557–560.

    PubMed  CAS  Google Scholar 

  160. Vacca F, Bagnato A, Catt KJ, Tecce R. Transactivation of the epidermal growth factor in endothelin-1 induced mitogenic signaling in human ovarian carcinoma cells. Cancer Res 2000; 60: 5310–5317.

    PubMed  CAS  Google Scholar 

  161. Yang Z, Krasnici N, Luscher T. Endothelin potentiates human smooth muscle cell growth to PDGF. Circulation 1999; 100: 5–8.

    PubMed  CAS  Google Scholar 

  162. Culig Z, Hobisch A, Cronauer MV, et al. Regulation of prostatic growth and function by peptide growth factors. Prostate 1996; 28: 392–405.

    PubMed  CAS  Google Scholar 

  163. Takuwa Y, Ohue Y, Takuwa N. Endothelin-1 activates phospholipase C and mobilizes Ca2+ from extra-and intracellular pools in osteoblastic cells. Am J Physiol 1989; 257: 797–803.

    Google Scholar 

  164. Takuwa Y, Masaki T, Yamashita K. The effects of the endothelin family peptides on cultured osteoblastic cells from rat calvariae. Biochem Biophys Res Commun 1990; 170: 998–1005.

    PubMed  CAS  Google Scholar 

  165. Tatrai A, Foster S, Lakatos P, et al. Endothelin-1 actions on resorption, collagen and noncollagen protein synthesis, and phosphatidylinositol turnover in bone organ cultures. Endocrinology 1992; 131: 603–607.

    PubMed  CAS  Google Scholar 

  166. Shioide M, Noda M. Endothelin modulates osteopontin and osteocalcin messenger ribonucleic acid expression in rat osteoblastic osteosarcoma cells. J Cell Biochem 1993; 53: 176–180.

    PubMed  CAS  Google Scholar 

  167. Chiao JW, Moonga BS, Yang YM, et al. Endothelin-1 from prostate cancer cells in enhanced by bone contact which blocks osteoclastic bone resorption. Br J Cancer 2000; 83: 360–365.

    PubMed  CAS  Google Scholar 

  168. Wu-Wong JR, Chiou WJ, Dickinson R, Opgenorth TJ. Endothelin attenuates apoptosis in human smooth muscle cells. Biochem J 1997; 328: 733–737.

    PubMed  CAS  Google Scholar 

  169. Salani D, Di Castro V, Nicotra MR, et al. Role of endothelin-1 in neovascularization of ovarian carcinoma. Am J Pathol 2000; 157: 1537–1547.

    PubMed  CAS  Google Scholar 

  170. Salani D, Garagoletti G, Rosano L, et al. Endothelin-1 induces an angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Am J Pathol 2000; 157: 1703–1711.

    PubMed  CAS  Google Scholar 

  171. Dahlof B, Gustafsson D, Hedner T, et al. Regional haemodynamic effects of endothelin-1 in rat and man: unexpected adverse reaction. J Hypertens 1990; 8: 811–817.

    PubMed  CAS  Google Scholar 

  172. Yoshizawa T, Kimura S, Kanazawa I, et al. Endothelin localizes in the dorsal horn and acts on the spinal cord neurons: possible involvement of dihydropyridine-sensitive calcium channels and substance P release. Neurosci Lett 1989; 102: 179–184.

    PubMed  CAS  Google Scholar 

  173. Raffa RB, Schupsky JJ, Jacoby HI. Endothelin-induced nociception in mice: mediation by ETA and ETB receptors. J Pharmacol Exp Ther 1996; 276: 647–651.

    PubMed  CAS  Google Scholar 

  174. Carducci MA, Nelson JB, Bowling MK, et al. Atrasentan, an endothelin-receptor antagonist for refractory adenocarcinomas: safety and pharmacokinetics. J Clin Oncol 2002; 20: 2171–2180.

    PubMed  CAS  Google Scholar 

  175. Carducci MA, Nelson JB, Humerickhouse R, et al. Effects of atrasentan on progression and survival in men with hormone refractory prostate cancer: follow-up to study M96–594. Proc Am Soc Clin Oncol 2002; 21: 708a.

    Google Scholar 

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Authors
  1. Evan Y. Yu
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  2. William C. Hahn
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  3. Daniel J. George
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  4. Philip W. Kantoff
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Editors and Affiliations

  1. Section of Urology Oncology, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

    Eric A. Klein MD (Head) (Head)

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Yu, E.Y., Hahn, W.C., George, D.J., Kantoff, P.W. (2004). Opportunities for Targeted Molecular Therapy for Prostate Cancer. In: Klein, E.A. (eds) Management of Prostate Cancer. Current Clinical Urology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-776-5_35

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  • DOI: https://doi.org/10.1007/978-1-59259-776-5_35

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