Systemic therapy of metastatic bladder cancer in the molecular era: Current status and future promise

Expert Opinion on Investigational Drugs

Volumn 19, Issue 7, 2010, Pages 875-887

  Zachos, Ioannis ^a   Konstantinopoulos, Panagiotis A ^b,c   Tzortzis, Vassilios ^a   Gravas, Stavros ^a   Karatzas, Anastasios ^a   Karamouzis, Michalis V ^b   Melekos, Michael ^a   Papavassiliou, Athanasios G ^b  

^a UNIVERSITY OF THESSALY   (Greece)

^b UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^c BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Antiangiogenic agents; Bladder cancer; Immune therapies; Molecular targeted agents; Systemic therapy; Tyrosine kinase inhibitors

Indexed keywords

AFLIBERCEPT; AURORA KINASE INHIBITOR; BEVACIZUMAB; CARBOPLATIN; CETUXIMAB; CISPLATIN; CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; ENDOTHELIN RECEPTOR ANTAGONIST; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; GEFITINIB; GEMCITABINE; IXABEPILONE; LAPATINIB; METHOTREXATE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PACLITAXEL; PAZOPANIB; PEMETREXED; PLACEBO; SORAFENIB; SUNITINIB; TRASTUZUMAB; UNINDEXED DRUG; VANDETANIB; VASCULOTROPIN; VINBLASTINE; VINFLUNINE;

ABDOMINAL PAIN; ADJUVANT THERAPY; ANOREXIA; BLADDER CANCER; BLEEDING; BONE MARROW SUPPRESSION; CANCER CELL CULTURE; CANCER MORTALITY; CANCER RADIOTHERAPY; CANCER SURVIVAL; CARCINOGENESIS; CLINICAL TRIAL; CYSTECTOMY; DIARRHEA; DISEASE FREE SURVIVAL; DRUG FATALITY; DRUG POTENTIATION; DRUG TARGETING; FATIGUE; FEBRILE NEUTROPENIA; GASTROINTESTINAL DISEASE; HAND FOOT SYNDROME; HEART DISEASE; HUMAN; HYPERTENSION; KARNOFSKY PERFORMANCE STATUS; METASTASIS POTENTIAL; MUCOSA INFLAMMATION; OVERALL SURVIVAL; PROGNOSIS; QT PROLONGATION; RASH; REVIEW; SIGNAL TRANSDUCTION; SKIN ULCER; THROMBOSIS; TREATMENT OUTCOME; VOMITING;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CLINICAL TRIALS, PHASE II AS TOPIC; DISEASE-FREE SURVIVAL; HUMANS; NEOPLASM METASTASIS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECEPTOR, EPIDERMAL GROWTH FACTOR; URINARY BLADDER NEOPLASMS; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 77953403675     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.2010.496450     Document Type: Review

References (111)

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin 2009;19(4):225-249
2. Dinney CP. Therapy of invasive bladder cancer. Urology 2006;67(3 Suppl 1):56-9; discussion 60-61
3. Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 2001;19(3):666-675
4. Bajorin DF, Dodd PM, Mazumdar M, et al. Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol 1999;17(10):3173-3181
5. Von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000;18(17):3068-3077
6. Culine S, Theodore C, De Santis M, et al. A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. Br J Cancer 2006;94(10):1395-1401
7. Logothetis CJ, Dexeus FH, Finn L, et al. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol 1990;8(6):1050-1055
8. Loehrer PJ Sr, Einhorn LH, Elson PJ, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol 1992;10(7):1066-1073
9. Sternberg CN, Calabro F, Pizzocaro G, et al. Chemotherapy with an every-2-week regimen of gemcitabine and paclitaxel in patients with transitional cell carcinoma who have received prior cisplatin-based therapy. Cancer 2001;92(12):2993-2998
10. Siefker-Radtke AO, Millikan RE, Tu SM, et al. Phase III trial of fluorouracil, interferon alpha-2b, and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in metastatic or unresectable urothelial cancer. J Clin Oncol 2002;20(5):1361-1367
11. Bamias A, Aravantinos G, Deliveliotis C, et al. Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group. J Clin Oncol 2004;22(2):220-228
12. Dreicer R, Manola J, Roth BJ, et al. Phase III trial of methotrexate, vinblastine, doxorubicin, and cisplatin versus carboplatin and paclitaxel in patients with advanced carcinoma of the urothelium. Cancer 2004;100(8):1639-1645
13. Von der Maase H, Sengelov L, Roberts JT, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 2005;23(21):4602-4608
14. National Comprehensive Cancer Network (NCCN) website. Available at www.nccn.org
15. Bellmunt J, Albiol S, Kataja V. Invasive bladder cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008;19(Suppl 2):ii47-8
16. Bellmunt J, von der Maase H, Mead GM, et al. Randomized phaseIII study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy. EORTC30987/Intergroup Study [abstract LBA5030]. 2007 Asco Annual Meeting Proceedings; 1-5 June; Chicago, IL, USA; J Clin Oncol 2007
17. Saxman SB, Propert KJ, Einhorn LH, et al. Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol 1997;15(7):2564-2569
18. Bachner M, De Santis M. Second-line therapy in bladder cancer. Curr Opin Urol 2009;19(5):533-539
19. Gallagher DJ, Milowsky MI, Bajorin DF. Advanced bladder cancer: status of first-line chemotherapy and the search for active agents in the second-line setting. Cancer 2008;113(6):1284-1293
20. Dreicer R, Li S, Manola J, et al. Phase 2 trial of epothilone B analog BMS-247550 (ixabepilone) in advanced carcinoma of the urothelium (E3800): a trial of the Eastern Cooperative Oncology Group. Cancer 2007;110(4):759-763
21. Sweeney CJ, Roth BJ, Kabbinavar FF, et al. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol 2006;24(21):3451-3457
22. Bellmunt J, Theodore C, Demkov T, et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol 2009;27(27):4454-4461
23. Garcia JA, Dreicer R. Systemic chemotherapy for advanced bladder cancer: update and controversies. J Clin Oncol 2006;24(35):5545-5551
24. Rajkumar T, Stamp GW, Pandha HS, et al. Expression of the type 1 tyrosine kinase growth factor receptors EGF receptor, c-erbB2 and c-erbB3 in bladder cancer. J Pathol 1996;179(4):381-385
25. Philips GK, Halabi S, Sanford BL, et al. A phase II trial of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial tract carcinoma: results of Cancer and Leukemia Group B (CALGB) 90102. Ann Oncol 2009;20(6):1074-1079
26. Sriplakich S, Jahnson S, Karlsson MG. Epidermal growth factor receptor expression: predictive value for the outcome after cystectomy for bladder cancer? BJU Int 1999;83(4):498-503
27. Dominguez-Escrig JL, Kelly JD, Neal DE, et al. Evaluation of the therapeutic potential of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in preclinical models of bladder cancer. Clin Cancer Res 2004;10(14):4874-4884
28. Neal DE, Sharples L, Smith K, et al. The epidermal growth factor receptor and the prognosis of bladder cancer. Cancer 1990;65(7):1619-1625
29. Petrylak D, Faulkner JR, Van Veldhuizen PJ, et al. New York Presbyterian Hospital, New York, NY; Southwest Oncology Group Statistical Center, Seattle, WA; Veterans Affairs Medical Center, Kansas City, MO; University of Colorado, Denver, CO. Evaluation of ZD1839 for advanced transitional cell carcinoma (TCC) of the urothelium: A Southwest Oncology Group Trial. Proc Am Soc Clin Oncol: 2003;22: abstract 1619
30. MDAC: M D. Anderson Cancer Center: Iressa and Taxotere Study in patients with metastatic urothelial cancer. ClinicalTrialsgov Identifier: NCT00479089
31. Jin Y, Iwata KK, Belldegrun A, et al. Effect of an epidermal growth factor receptor tyrosine kinase inhibitor on actin remodeling in an in vitro bladder cancer carcinogenesis model. Mol Cancer Ther 2006;5(7):1754-1763
32. Pruthi RS, Nielsen M, Heathcote S, et al. A phase II trial of neoadjuvant erlotinib in patients with muscle-invasive bladder cancer undergoing radical cystectomy: clinical and pathologicalresults. BJU Int 2010. [Epub ahead of print]
33. Perrotte P, Matsumoto T, Inoue K, et al. Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin Cancer Res 1999;5(2):257-265
34. Inoue K, Slaton JW, Perrotte P, et al. Paclitaxel enhances the effects of the anti-epidermal growth factor receptor monoclonal antibody ImClone C225 in mice with metastatic human bladder transitional cell carcinoma. Clin Cancer Res 2000;6(12):4874-4884 (Pubitemid 32110432)
35. Michigan University: Study of gemcitabine and cisplatin with or without cetuximab in urothelial cancer. Clinical-Trials.gov identifier NCT00645593. US National Institutes of Health
36. Jimenez RE, Hussain M, Bianco FJ Jr, et al. Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors. Clin Cancer Res 2001;7(8):2440-2447
37. Hussain MH, MacVicar GR, Petrylak DP, et al. Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial. J Clin Oncol 2007;25(16):2218-2224
38. RTOG: Radiation Therapy Oncology Group. Paclitaxel and radiation therapy with or without trastuzumab in treating patients who have undergone surgery for bladder cancer. ClinicalTrialsgov Identifier: NCT00238420
39. Clark TW, Cohen RA, Kwak A, et al. Salvage of nonmaturing native fistulas by using angioplasty. Radiology 2007;242(1):286-292
40. Beuzeboc P, Banu E, Voog E, et al. Trastuzumab (T) combined with standard chemotherapy in HER+ metastatic bladder cancer (BC) patients: Interim safety results of a prospective randomized phase II study. 2007 ASCO Annual Meeting Proceedings Part I. J Clin Oncol 2007;25(18S):15565
41. Medina PJ, Goodin S. Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther 2008;30(8):1426-1447
42. McHugh LA, Sayan AE, Mejlvang J, et al. Lapatinib, a dual inhibitor of ErbB-1/-2 receptors, enhances effects of combination chemotherapy in bladder cancer cells. Int J Oncol 2009;34(4):1155-1163
43. Wulfing C, Machiels JP, Richel DJ, et al. A single-arm, multicenter, open-label phase 2 study of lapatinib as the second-line treatment of patients with locally advanced or metastatic transitional cell carcinoma. Cancer 2009;115(13):2881-2890
44. Orchid Clinical Trials Group at Barts and the London School of Medicine and Dentistry. Lapatinib ditosylate in treating patients with stage IV bladder cancer. ClinicalTrialsgov Identifier: NCT00949455
45. Galsky MD, Von Hoff DD, Neubauer M, et al. Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors. 2009 ASCO Annual meeting. J Clin Oncol 2009;27(15s): abstract 3541
46. Korkolopoulou P KA, Kavantzas N, Patsouris E, et al. Morphometric microvascular characteristics predict prognosis in superficial and invasive bladder cancer. Virchows Arch 2001;438:603-611
47. Stein JP, Grossfeld GD, Ginsberg DA, et al. Prognostic markers in bladder cancer: a contemporary review of the literature. J Urol 1998;160(3 Pt 1):645-659
48. Shao ZM, Nguyen M. Angiogenic factors and bladder cancer. Front Biosci 2002;7:e33-5
49. Bernardini S, Fauconnet S, Chabannes E, et al. Serum levels of vascular endothelial growth factor as a prognostic factor in bladder cancer. J Urol 2001;166(4):1275-1279
50. Jones A, Crew J. Vascular endothelial growth factor and its correlation with superficial bladder cancer recurrence rates and stage progression. Urol Clin North Am 2000;27(1):191-197
51. Chopin DK, Caruelle JP, Colombel M, et al. Increased immunodetection of acidic fibroblast growth factor in bladder cancer, detectable in urine. J Urol 1993;150(4):1126-1130
52. O'Brien TS, Smith K, Cranston D, et al. Urinary basic fibroblast growth factor in patients with bladder cancer and benign prostatic hypertrophy. Br J Urol 1995;76(3):311-314
53. Gravas S, Bosinakou I, Kehayas P, Giannopoulos A. Urinary basic fibroblast growth factor in bladder cancer patients. Histopathological correlation and clinical potential. Urol Int 2004;73(2):173-177
54. Folkman J. Seminars in medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med 1995;333(26):1757-1763
55. Mitra AP, Lin H, Datar RH, Cote RJ. Molecular biology of bladder cancer: prognostic and clinical implications. Clin Genitourin Cancer 2006;5(1):67-77
56. Inoue K, Slaton JW, Karashima T, et al. The prognostic value of angiogenesis factor expression for predicting recurrence and metastasis of bladder cancer after neoadjuvant chemotherapy and radical cystectomy. Clin Cancer Res 2000;6(12):4866-4873
57. Yang CC, Chu KC, Yeh WM. The expression of vascular endothelial growth factor in transitional cell carcinoma of urinary bladder is correlated with cancer progression. Urol Oncol 2004;22(1):1-6
58. Medical University of South Carolina: Cisplatin, Bevacizumab, and Gemcitabine Followed by Surgery, Bevacizumab, and Paclitaxel in treating patients with locally advanced nonmetastatic bladder cancer that can be removed by surgery. June 2009. ClinicalTrials.gov Identifier: NCT00268450
59. Hahn NM, Stadler WM, Zon RT, Waterhouse DM. A multicenter phase II study of cisplatin (C), gemcitabine (G), and bevacizumab (B) as first-line chemotherapy for metastatic urothelial carcinoma (UC): Hoosier Oncology Group GU-0475. 2009 ASCO Annual Meeting J Clin Oncol 2009;27(15s): abstract 5018
60. CALG: Cancer Leucemia Group B Gemcitabine Hydrochloride and Cisplatin with or without bevacizumab in treating patients with advanced urinary tract cancer. ClinicalTrialsgov Identifier: NCT00942331
61. Chu QS. Aflibercept (AVE0005): an alternative strategy for inhibiting tumour angiogenesis by vascular endothelial growth factors. Expert Opin Biol Ther 2009;9(2):263-271
62. Twardowski P, StadlerW M, Frankel P, et al. Phase II study of aflibercept (VEGF-Trap) in patients (pts) with recurrent or metastatic transitional cell carcinoma (TCC) of the urothelium. A California Cancer Consortium trial. J Clin Oncol 2009;27:abstract e16030
63. Sonpavde G, Jian W, Liu H, et al. Sunitinib malate is active against human urothelial carcinoma and enhances the activity of cisplatin in a preclinical model. Urol Oncol 2009;27(4):391-399
64. Gallagher DJ, Milowsky MI, Gerst SR, et al. Phase II study of sunitinib in patients with metastatic urothelial cancer. J Clin Oncol 2010;28(8):1373-1379
65. Gallagher DJ, MIlowsky MI, GerstS RS, et al. A phase II study of sunitinib on a continuous dosing schedule in patients (pts) with relapsed or refractory urothelial carcinoma (UC). 2009 ASCO Annual Meeting. J Clin Oncol 2009;27(15s): abstract 5072
66. Bellmunt J MP, Mellado B, Carles J, et al. Phase II study of sunitinib as first line treatment in aptients with advanced urothelial cancer ineligible for cisplatin-based chemotherapy. Genitourin Cancer Symp 2008:abstract 291
67. Bradley D, Daignault S, Smith DC, et al. 2009 ASCO Annual Meeting. J Clin Oncol 2009;27(15s): abstract 5073
68. Mackenzie MJ, Winquist E, Rodrigues G. Open clinical uro-oncology trials in Canada. Can J Urol 2010;17(1):5050-5056
69. Available from: http://clinicaltrials.gov/ct2/show/NCT00859339, Hoosier Oncology Group HOG. Neoadjuvant cisplatin, gemcitabine, sunitinib malate + radical cystectomy for transitional cell carcinoma (TCC) of the bladder MS-KC: Memorial Sloan-Kettering Cancer Center: gemcitabine, cisplatin, and sunitinib (GC-S) as neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer. ClinicalTrialsgov Identifier: NCT00847015
70. Dreicer R, Li H, Stein M, et al. Phase 2 trial of sorafenib in patients with advanced urothelial cancer: a trial of the Eastern Cooperative Oncology Group. Cancer 2009;115(18):4090-4095
71. Sridhar SS, Winquist E, Eisen A, et al. A phase II study of first-line sorafenib (Bay 43-9006) in advanced or metastatic urothelial cancer. A trial of the PMH Phase II Consortium [abstract]. 2008 Genitourin Cancer Symp
72. Sonpavde G, Sternberg CN. Treatment of metastatic urothelial cancer: opportunities for drug discovery and development. BJU Int 2008;102(9 Pt B):1354-1360
73. Hurwitz HI, Dowlati A, Saini S, et al. Phase I trial of pazopanib in patients with advanced cancer. Clin Cancer Res 2009;15(12):4220-4227
74. Mayo Clinic: pazopanib in treating patients with metastatic urothelial cancer. ClinicalTrials.gov Identifier: NCT00471536
75. Holden SN, Eckhardt SG, Basser R, et al. Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors. Ann Oncol 2005;16(8):1391-1397
76. Flaig TW, Su LJ, McCoach C, et al. Dual epidermal growth factor receptor and vascular endothelial growth factor receptor inhibition with vandetanib sensitizes bladder cancer cells to cisplatin in a dose-and sequence-dependent manner. BJU Int 2009;103(12):1729-1737
77. Dana-Farber Cancer Institute: docetaxel with or without vandetanib in treating patients with previously treated stage IV transitional cell cancer. ClinicalTrials.gov Identifier: NCT00378794
78. Gromet MA, Epstein WL, Blois MS. The regressing thin malignant melanoma: a distinctive lesion with metastatic potential. Cancer 1978;42(5):2282-2292
79. Knuth A, Wolfel T, Klehmann E, et al. Cytolytic T-cell clones against an autologous human melanoma: specificity study and definition of three antigens by immunoselection. Proc Natl Acad Sci USA 1989;86(8):2804-2808
80. Wolfel T, Klehmann E, Muller C, et al. Lysis of human melanoma cells by autologous cytolytic T cell clones. Identification of human histocompatibility leukocyte antigen A2 as a restriction element for three different antigens. J Exp Med 1989;170(3):797-810
81. Blansfield JA, Beck KE, Tran K, et al. Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J Immunother 2005;28(6):593-598
82. Korman A, Yellin M, Keler T. Tumor immunotherapy: preclinical and clinical activity of anti-CTLA4 antibodies. Curr Opin Investig Drugs 2005;6(6):582-591
83. Peggs KS, Quezada SA, Allison JP. Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol Rev 2008;224:141-165
84. Sun J, Schiffman J, Raghunath A, et al. Concurrent decrease in IL-10 with development of immune-related adverse events in a patient treated with anti-CTLA-4 therapy. Cancer Immun 2008;8:9
85. Zhou H, Kuang J, Zhong L, et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet 1998;20(2):189-193
86. Bischoff JR, Anderson L, Zhu Y, et al. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. Embo J 1998;17(11):3052-3065
87. Pugacheva EN, Golemis EA. The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome. Nat Cell Biol 2005;7(10):937-946
88. Park HS, Park WS, Bondaruk J, et al. Quantitation of Aurora kinase A gene copy number in urine sediments and bladder cancer detection. J Natl Cancer Inst 2008;100(19):1401-1411
89. Faivre S, Djelloul S, Raymond E. New paradigms in anticancer therapy: targeting multiple signaling pathways with kinase inhibitors. Semin Oncol 2006;33(4):407-420
90. Dalbagni G, Presti J, Reuter V, et al. Genetic alterations in bladder cancer. Lancet 1993;342(8869):469-471
91. Konstantinopoulos PA, Karamouzis MV, Papavassiliou AG. Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nat Rev Drug Discov 2007;6(7):541-555
92. Winquist E, Moore MJ, Chi KN, et al. A multinomial Phase II study of lonafarnib (SCH 66336) in patients with refractory urothelial cancer. Urol Oncol 2005;23(3):143-149
93. Theodore C, Geoffrois L, Vermorken JB, et al. Multicentre EORTC study 16997: feasibility and phase II trial of farnesyl transferase inhibitor & gemcitabine combination in salvage treatment of advanced urothelial tract cancers. Eur J Cancer 2005;41(8):1150-1157
94. Konstantinopoulos PA, Papavassiliou AG. 17-AAG: mechanisms of antitumour activity. Expert Opin Investig Drugs 2005;14(12):1471-1474
95. Wang JY, Wilcoxen KM, Nomoto K, Wu S. Recent advances of MEK inhibitors and their clinical progress. Curr Top Med Chem 2007;7(14):1364-1378
96. Li N, Batt D, Warmuth M. B-Raf kinase inhibitors for cancer treatment. Curr Opin Investig Drugs 2007;8(6):452-456
97. Nelson J, Bagnato A, Battistini B, Nisen P. The endothelin axis: emerging role in cancer. Nat Rev Cancer 2003;3(2):110-116
98. Wulfing C, Eltze E, Piechota H, et al. Expression of endothelin-1 and endothelin-A and-B receptors in invasive bladder cancer. Oncol Rep 2005;13(2):223-228
99. Wulfing C, Eltze E, Yamini J, et al. Expression of the endothelin axis in bladder cancer: relationship to clinicopathologic parameters and long-term survival. Eur Urol 2005;47(5):593-600
100. Herrmann E, Bogemann M, Bierer S, et al. The role of the endothelin axis and microvessel density in bladder cancer-correlation with tumor angiogenesis and clinical prognosis. Oncol Rep 2007;18(1):133-138
101. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407(6801):249-257
102. Mita AC, Wang D, Takimoto CH, et al. Amg 386, a selective angiopoietin 1/2-neutralizing peptibody, in combination with chemotherapy in adult patients with advanced solid tumors. Meeting abstracts. J Clin Oncol 2007;25:14033
103. Cappellen D, De Oliveira C, Ricol D, et al. Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet 1999;23(1):18-20
104. Novartis Pharmaceuticals. Phase II Study of TKI258 in Advanced Urothelial Carcinoma. ClinicalTrialsgov Identifier: NCT00790426
105. Sridhar SS, Canil CM, Mukherjee SD, et al. Princess Margaret Hospital, Toronto, ON, Canada; Ottawa Regional Cancer Center, Ottawa, ON, Canada; Juravinski Cancer Centre, Hamilton, ON, Canada; London Regional Cancer Centre, London, ON, Canada; Sunnybrook Odette Cancer Centre, Toronto, ON, Canada A phase II study of single-agent nab-paclitaxel as second-line therapy in patients with metastatic urothelial carcinoma. ASCO Annual Meeting 2010
106. Takai N, Hamanaka R, Yoshimatsu J, Miyakawa I. Polo-like kinases (Plks) and cancer. Oncogene 2005;24(2):287-291
107. Boehringer Ingelheim Pharmaceuticals. Intravenous BI 6727 in 2nd Line Treatment of Urothelial Cancer. ClinicalTrialsgov Identifier: NCT01023958
108. Brunton VG, Frame MC. Src and focal adhesion kinase as therapeutic targets in cancer. Curr Opin Pharmacol 2008;8(4):427-432
109. Johnson FM, Saigal B, Talpaz M, Donato NJ. Dasatinib (BMS-354825) tyrosine kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma and non-small cell lung cancer cells. Clin Cancer Res 2005;11(19 Pt 1):6924-6932
110. Nam S, Kim D, Cheng JQ, et al. Action of the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate cancer cells. Cancer Res 2005;65(20):9185-9189
111. Levitt JM, Yamashita H, Jian W, et al. Dasatinib is preclinically active against Src-overexpressing human transitional cell carcinoma of the urothelium with activated Src signaling. Mol Cancer Ther 2010;9(5):1128-1135