Molecular signaling and the role of targeted therapies in bladder cancer

Minerva Urologica e Nefrologica

Volumn 64, Issue 1, 2012, Pages 7-17

  Black, P C ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Molecular targeted therapy; Receptors, growth factor; Urinary bladder neoplasms

Indexed keywords

AFATINIB; AZD 4547; AZD 7762; BEVACIZUMAB; CARBOPLATIN; CETUXIMAB; CG 0070; CISPLATIN; CONTUSUGENE LADENOVEC; DACOMITINIB; DOCETAXEL; DOVITINIB; DOXORUBICIN; ERLOTINIB; EVEROLIMUS; GEFITINIB; GEMCITABINE; GENDICINE; LAPATINIB; METHOTREXATE; NERATINIB; OGX 427; PACLITAXEL; PAZOPANIB; PF 00477736; RAPAMYCIN; SORAFENIB; SUNITINIB; TEMSIROLIMUS; TRASTUZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANDETANIB; VASCULOTROPIN; VINBLASTINE; XL 647; XL 844;

ADVANCED CANCER; BLADDER CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER RESISTANCE; DRUG TOLERABILITY; GENE OVEREXPRESSION; METASTASIS; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; REVIEW; SIGNAL TRANSDUCTION; TRANSITIONAL CELL CARCINOMA; TREATMENT RESPONSE;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; CELL TRANSFORMATION, NEOPLASTIC; CLINICAL TRIALS AS TOPIC; HUMANS; MOLECULAR TARGETED THERAPY; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-MET; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA; RECEPTORS, FIBROBLAST GROWTH FACTOR; SIGNAL TRANSDUCTION; TREATMENT OUTCOME; URINARY BLADDER NEOPLASMS; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VIRAL VACCINES;

EID: 84860271855     PISSN: 03932249     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (100)

1. Spiess PE, Czerniak B: Dual-track pathway of bladder carcinogenesis: practical implications. Arch Pathol Lab Med 2006;130:844-52. (Pubitemid 43887006)
2. Kassouf W, Black PC, Tuziak T, Bondaruk J, Lee S, Brown GA, Adam L et al. Distinctive expression pattern of ErbB family receptors signifies an aggressive variant of bladder cancer. J Urol 2008;179:353-8. (Pubitemid 350216717)
3. Sriplakich S, Jahnson S, Karlsson MG. Epidermal growth factor receptor expression: predictive value for the outcome after cystectomy for bladder cancer? BJU Int 1999;83:498-503. (Pubitemid 29151180)
4. Mellon K, Wright C, Kelly P, Home CH, Neal DE. Long-term outcome related to epidermal growth factor receptor status in bladder cancer. J Urol 1995;153:919-25.
5. Kassouf W, Dinney CP, Brown G, McConkey DJ, Diehl AJ, Bar-Eli M et al. Uncoupling between epidermal growth factor receptor and downstream signals defines resistance to the antiproliferative effect of Gefitinib in bladder cancer cells. Cancer Res 2005;65:10524-35. (Pubitemid 41748146)
6. Kassouf W, Luongo T, Brown G, Adam L, Dinney CP. Schedule dependent efficacy of gefitinib and docetaxel for bladder cancer. J Urol 2006;176:787-92. (Pubitemid 43927919)
7. Ciardiello F, Caputo R, Bianco R, Damiano V, Pomatico G, De Placido S 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;6:2053-63. (Pubitemid 30305105)
8. Inoue K, Slaton JW, Perrotte P, Davis DW, Bruns CJ, Hicklin DJ 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;6:4874-84. (Pubitemid 32110432)
9. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123-32. (Pubitemid 41058344)
10. Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A et al. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 2005;23:5892-9.
11. Cunningham D, Humblet Y, Siena S, et al: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337-45, 2004 (Pubitemid 38944402)
12. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S et al. Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC-CTG]. J Clin Oncol 2007;25:1960-6. (Pubitemid 46972777)
13. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78. (Pubitemid 43209104)
14. Philips GK, Halabi S, Sanford BL, Bajorin D, Small EJ; Cancer and Leukaemia Group B. A phase II trial of cisplatin, fixed dose-rate gemcitabine and gefitinib for advanced urothelial tract carcinoma: results of the Cancer and Leukaemia Group B 90102. BJU Int 2008;101:20-5. (Pubitemid 350233568)
15. Philips GK, Halabi S, Sanford BL, Bajorin D, Small EJ; Cancer and Leukemia Group B. 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;20:1074-9.
16. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al. EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy. Science 2004;304:1497-500. (Pubitemid 38720929)
17. L Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-39.
18. Ji H, Zhao X, Yuza Y, Shimamura T, Li D, Protopopov A et al. Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2006;103:7817-22.
19. Black PC, Brown GA, Inamoto T, Shrader M, Arora A, Siefker-Radtke AO et al. Sensitivity to epidermal growth factor receptor inhibitor requires E-cadherin expression in urothelial carcinoma cells. Clin Cancer Res 2008;14:1478-86. (Pubitemid 351413932)
20. S Shrader M, Pino MS, Brown G, Black P, Adam L, Bar-Eli M et al. Molecular correlates of gefitinib responsiveness in human bladder cancer cells. Mol Cancer Ther 2007;6:277-85.
21. McConkey DJ, Svatek R, Siefker-Radtke A. HDAC inhibitors reverse epithelial-to-mesenchymal transition (EMT) and restore sensitivity to EGFR inhibitors in urothelial carcinoma cells. ASCO Genitourinary Cancers Symposium 2009.
22. Vallo S, Xi W, Hudak L, Juengel E, Tsaur I, Wiesner C et al. HDAC inhibition delays cell cycle progression of human bladder cancer cells in vitro. Anti-Cancer Drugs 2011;22:1002-9.
23. Lammers RJ, Witjes JA: Discussion on the influence of HER2 status on the clinical outcome of bladder cancer continues. Expert Rev Anticancer Ther 2011;11:853-8.
24. Jimenez RE, Hussain M, Bianco FJ Jr, Vaishampayan U, Tabazcka P, Sakr WA 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;7:2440-7. (Pubitemid 32751647)
25. Mellon JK, Lunec J, Wright C, Home CH, Kelly P, Neal DE. C-erbB-2 in bladder cancer: molecular biology, correlation with epidermal growth factor receptors and prognostic value. J Urol 1996;155:321-6. (Pubitemid 126426487)
26. Krüger S, Weitsch G, Büttner H, Matthiensen A, Böhmer T, Marquardt T et al. HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications. Int J Cancer 2002;102:514-8. (Pubitemid 35316007)
27. Gandour-Edwards R, Lara PN Jr, Folkins AK, LaSalle JM, Beckett L, Li Y et al. Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma? Cancer 2002;95:1009-15. (Pubitemid 34925350)
28. Bolenz C, Shariat SF, Karakiewicz PI, Ashfaq R, Ho R, Sagalowsky AI et al. Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. BJU Int 2010;106:1216-22.
29. Laé M, Couturier J, Oudard S, Radvanyi F, Beuzeboc P, Vieillefond A. Assessing HER2 gene amplification as a potential target for therapy in invasive urothelial bladder cancer with a standardized methodology: results in 1005 patients. Ann Oncol 2010;21:815-9.
30. Fleischmann A, Rotzer D, Seiler R, Studer UE, Thalmann GN. Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours. Eur Urol 2011;60:350-7.
31. Hansel DE, Swain E, Dreicer R, Tubbs RR. HER2 overexpression and amplification in urothelial carcinoma of the bladder is associated with MYC coamplification in a subset of cases. Am J Clin Pathol 2008;130:274-81.
32. Hussain MH, MacVicar GR, Petrylak DP, Dunn RL, Vaishampayan U, Lara PN Jr 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;25:2218-24. (Pubitemid 46954646)
33. McHugh LA, Sayan AE, Mejlvang J, Griffiths TR, Sun Y, Manson MM et al. Lapatinib, a dual inhibitor of ErbB-1/-2 receptors, enhances effects of combination chemotherapy in bladder cancer cells. Int J Oncol 2009;34:1155-63.
34. McHugh LA, Kriajevska M, Mellon JK, Griffiths TR. Combined treatment of bladder cancer cell lines with iapatinib and varying chemotherapy regimens - evidence of schedule-dependent synergy. Urology 2007;69:390-4. (Pubitemid 46274953)
35. Quesnelle KM, Grandis JR. Dual kinase inhibition of EGFR and HER2 overcomes resistance to cetuximab in a novel in vivo model of acquired cetuximab resistance. Clin Cancer Res 2011;17:5935-44.
36. Wülfing C, Machiels JP, Richel DJ, Grimm MO, Treiber U, De Groot MR 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;115:2881-90.
37. Hernández S, López-Knowles E, Lloreta J, Kogevinas M, Amorós A, Tardón A et al. Prospective Study of FGFR3 Mutations As a Prognostic Factor in Nonmuscle Invasive Urothelial Bladder Carcinomas. J Clin Oncol 2006;24:3664-71. (Pubitemid 46630542)
38. Sibley K, Cuthbert-Heavens D, Knowles MA. Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma. Oncogene 2001;20:686-91. (Pubitemid 32179337)
39. Billerey C, Chopin D, Aubriot-Lorton MH. Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol 2011;158:1955-9.
40. L'Hote CG, Knowles MA. Cell responses to FGFR3 signalling: growth, differentiation and apoptosis. Exp Cell Res 2005;304:417-31. (Pubitemid 40321120)
41. Gómez-Román JJ, Saenz P, Molina M, Cuevas González J, Escuredo K, Santa Cruz S et al. Fibroblast growth factor receptor 3 is overexpressed in urinary tract carcinomas and modulates the neoplastic cell growth. Clin Cancer Res 2005;11:459-65. (Pubitemid 40116867)
42. van Rhijn BW, Lurkin I, Radvanyi F, Kirkels WJ, van der Kwast TH, Zwarthoff EC. The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer Res 2001;61:1265-8. (Pubitemid 34292538)
43. van Rhijn BW, Zuiverloon TC, Vis AN, Radvanyi F, van Leenders GJ, Ooms BC et al. Molecular grade (FGFR3/MIB-1) and EORTC risk scores are predictive in primary non-muscle-invasive bladder cancer. Eur Urol 2010;58:433-41.
44. Burger M, van der Aa MN, van Oers JM, Brinkmann A, van der Kwast TH, Steyerberg EC. Prediction of progression of non-muscle-invasive bladder cancer by WHO 1973 and 2004 grading and by FGFR3 mutation status: a prospective study. Eur Urol 2008;54:835-43.
45. van Rhijn BW, Vis AN, van der Kwast TH, Kirkels WJ, Radvanyi F, Ooms EC et al. Molecular grading of urothelial cell carcinoma with fibroblast growth factor receptor 3 and MIB-1 is superior to pathologic grade for the prediction of clinical outcome. J Clin Oncol 2003;21:1912-21. (Pubitemid 46606378)
46. Goebell PJ, Knowles MA: Bladder cancer or bladder cancers? Genetically distinct malignant conditions of the urothelium. Urol Oncol 2010;28:409-28.
47. Tomlinson DC, Hurst CD, Knowles MA: Knockdown by shRNA identifies S249C mutant FGFR3 as a potential therapeutic target in bladder cancer. Oncogene 2007;26:5889-99.
48. Lamont FR, Tomlinson DC, Cooper PA, Shnyder SD, Chester JD, Knowles MA. Small molecule FGF receptor inhibitors block FGFR-dependent urothelial carcinoma growth in vitro and in vivo. Br J Cancer 2011;104:75-82.
49. Gust K, McConkey DJ, Hegarty PK. Targeting Fibroblast Growth Factor Receptor (FGFR)-3 in bladder cancer: pre-clinical proof of principle. Annual Meeting of the American Association of Cancer Research 2011.
50. Miyata Y, Sagara Y, Kanda S, Hayashi T, Kanetake H. Phosphorylated hepatocyte growth factor receptor/c-Met is associated with tumor growth and prognosis in patients with bladder cancer: correlation with matrix metalloproteinase-2 and -7 and E-cadherin. Hum Pathol 2009;40:496-504.
51. Wang P, Nishitani MA, Tanimoto S, Kishimoto T, Fukumori T, Takahashi M et al. Bladder cancer cell invasion is enhanced by cross-talk with fibroblasts through hepatocyte growth factor. Urology 2007;69:780-4. (Pubitemid 46574944)
52. Yeh CY, Shin SM, Yeh HH, Wu TJ, Shin JW, Chang TY et al. Transcriptional activation of the Axl and PDGFR-alpha by c-Met through a ras- and Src-independent mechanism in human bladder cancer. BMC Cancer 2011;11:139.
53. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W et al. Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer. N Engl J Med 2004;350:2335-42. (Pubitemid 38702844)
54. Miller KD, Wang M, Gralow J. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100). Breast Cancer Res Treat 2005,94:S6.
55. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A et al. Paclitaxel-Carboplatin Alone or with Bevacizumab for Non-Small-Cell Lung Cancer. N Engl J Med 2006;355:2542-50. (Pubitemid 44917502)
56. Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentmber DJ, Topalian SL et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003;349:427-34. (Pubitemid 36910021)
57. Slaton JW, Millikan R, Inoue K, Karashima T, Czerniak B, Shen Y et al. Correlation of metastasis related gene expression and relapse-free survival in patients with locally advanced bladder cancer treated with cystectomy and chemotherapy. J Urol 2004;171:570-4. (Pubitemid 38090431)
58. Shah JB, McConkey DJ, Dinney CP: New strategies in muscle-invasive bladder cancer: on the road to personalized medicine. Clin Cancer Res 2011;17:2608-12.
59. Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349:859-66. (Pubitemid 37025405)
60. Pasche B. A new strategy in the war on renal cell cancer: hitting multiple targets with limited collateral damage. JAMA 2006;295:2537-38. (Pubitemid 43854970)
61. Kane RC, Farrell AT, Saber H, Tang S, Williams G, Jee JM et al. Sorafenib for the treatment of advanced renal cell carcinoma. Clin Cancer Res 2006;12:7271-8. (Pubitemid 46095398)
62. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H et al. BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis. Cancer Res 2004,64:7099-109. (Pubitemid 39331023)
63. Gallagher DJ, Milowsky MI, Gerst SR, et al: Phase II study of sunitinib in patients with metastatic urothelial cancer. J Clin Oncol 28:1373-9, 2010
64. Bellmunt J, González-Larriba JL, Prior C, Maroto P, Carles J, Castellano D et al. Phase II study of sunitinib as first-line treatment of urothelial cancer patients ineligible to receive cisplatin-based chemotherapy: baseline interleukin-8 and tumor contrast enhancement as potential predictive factors of activity. Ann Oncol 2011;22:2646-53.
65. Bradley DA, Dunn R, Nanus D, Stadler W, Dreicer R, Rosenberg J et al. Randomized, double-blind, placebo-controlled phase II trial of maintenance sunitinib versus placebo after chemotherapy for patients with advanced urothelial carcinoma: scientific rationale and study design. Clin Genitourin Cancer 2007;5:460-3. (Pubitemid 351219702)
66. Dreicer R, Li H, Stein M, DiPaola R, Eleff M, Roth BJ et al. Phase 2 trial of sorafenib in patients with advanced urothelial cancer. Cancer 2009;115:4090-5.
67. Sridhar SS, Winquist E, Eisen A, Hotte SJ, McWhirter E, Tannock IF et al. A phase II trial of sorafenib in first-line metastatic urothelial cancer: a study of the PMH Phase II Consortium. Investigational New Drugs 2011;29:1045-9.
68. Esrig D, Elmajian D, Groshen S, Freeman JA, Stein JP, Chen SC et al. Accumulation of nuclear p53 and tumor progression in bladder cancer. N Engl J Med 1994;331:1259-64. (Pubitemid 24333190)
69. Cote RJ, Esrig D, Groshen S, Jones PA, Skinner DG. p53 and treatment of bladder cancer. Nature 1997;385:123-5.
70. Stadler WM, Lerner SP, Groshen S, Stein JP, Shi SR, Raghavan D et al. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Oncol 2011;29:3443-9.
71. Kuball J, Wen SF, Leissner J, Atkins D, Meinhardt P, Quijano E et al. Successful adenovirus-mediated wild-type p53 gene transfer in patients with bladder cancer by intravesical vector instillation. J Clin Oncol 2002;20:957-65. (Pubitemid 34141838)
72. Pagliaro LC, Keyhani A, Williams D, Woods D, Liu B, Perrotte P et al. Repeated intravesical instillations of an adenoviral vector in patients with locally advanced bladder cancer: a phase I study of p53 gene therapy. J Clin Oncol 2003;21:2247-53. (Pubitemid 46621859)
73. Lambert JM, Gorzov P, Veprintsev DB, Söderqvist M, Segerbäck D, Bergman J et al. PRIMA-1 reactivates mutant p53 by covalent binding to the core domain. Cancer Cell 2009;15:376-88.
74. Wade M, Wahl GM. Targeting Mdm2 and Mdmx in Cancer Therapy: Better Living through Medicinal Chemistry? Molecular Cancer Research 2009;7:1-11.
75. Ambrosini G, Sambol EB, Carvajal D, Vassilev LT, Singer S, Schwartz GK. Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1. Oncogene 2007;26:3473-81. (Pubitemid 46816754)
76. Garrett MD, Collins I. Anticancer therapy with checkpoint inhibitors: what, where and when? Trends Pharmacol Sci 2011;32:308-16.
77. Zhang X, Multani AS, Zhou JH, Shay JW, McConkey D, Dong L et al. Adenoviral-mediated Retinoblastoma 94 Produces Rapid Telomere Erosion, Chromosomal Crisis, and Caspase-dependent Apoptosis in Bladder Cancer and Immortalized Human Urothelial Cells but not in Normal Urothelial Cells. Cancer Research 2003;63:760-5. (Pubitemid 36231972)
78. Pirollo KF, Rait A, Zhou Q, Zhang XQ, Zhou J, Kim CS et al. Tumor-targeting nanocomplex delivery of novel tumor suppressor RB94 chemosensitizes bladder carcinoma cells in vitro and in vivo. Clin Cancer Res 2008;14:2190-8. (Pubitemid 351551132)
79. Senzer N, Nemunaitis J, Goldstein M. A Phase 1 Dose-Escalation Trial of Intravesical CG0070 for Superficial Transitional Cell Carcinoma (TCC) of the Bladder after Bacillus Calmette-Guerin (BCG) Failure. Mol Ther 2006;13.S22.
80. Ching CB, Hansel DE. Expanding therapeutic targets in bladder cancer: the P13K/Akt/mTOR pathway. Lab Invest 2010;90:1406-14.
81. Chiong E, Lee IL, Dadbin A, Sabichi AL, Harris L, Urbauer D et al. Effects of mTOR inhibitor everolimus (RAD001) on bladder cancer cells. Clin Cancer Res 2011;17:2863-73.
82. Mansure JJ, Nassim R, Chevalier S, Rocha J, Scarlata E, Kassouf W. Inhibition of mammalian target of rapamycin as a therapeutic strategy in the management of bladder cancer. Cancer Biol Ther 2009;8:2339-47.
83. Garcia JA, Danielpour D. Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malignancies. Mol Cancer Ther 2008;7:1347-54.
84. Platt FM, Hurst CD, Taylor CF, Gregory WM, Hamden P, Knowles MA. Spectrum of phosphatidylinositol 3-kinase pathway gene alterations in bladder cancer. Clin Cancer Res 2009;15.6008-17.
85. Askham JM, Platt F, Chambers PA, Snowden H, Taylor CF, Knowles MA. AKT1 mutations in bladder cancer: identification of a novel oncogenic mutation that can co-operate with E17K. Oncogene 2010;29:150-5.
86. Pymar LS, Platt FM, Askham JM, Morrison EE, Knowles MA. Bladder tumour-derived somatic TSC1 missense mutations cause loss of function via distinct mechanisms. Hum Mol Genet 2008;17:2006-17. (Pubitemid 351865849)
87. Puzio-Kuter AM, Castillo-Martin M, Kinkade CW, Wang X, Shen TH, Matos T et al. Inactivation of p53 and Pten promotes invasive bladder cancer. Genes Dev 2009;23:675-80.
88. Kanda S, Kanetake H, Miyata Y Loss of PTEN function may account for reduced proliferation pathway sensitivity to LY294002 in human prostate and bladder cancer cells. J Cancer Res Clin Oncol 2009;135:303-11.
89. Wang X, Hawk N, Yue P, Kauh J, Ramalingam SS, Fu H et al. Overcoming mTOR inhibition-induced paradoxical activation of survival signaling pathways enhances mTOR inhibitors' anticancer efficacy. Cancer Biol Ther 2008;7:1952-8.
90. Matsui Y, Hadaschik BA, Fazli L, Andersen RJ, Gleave ME, So AI. Intravesical combination treatment with antisense oligonucleotides targeting heat shock protein-27 and HTI-286 as a novel strategy for high-grade bladder cancer. Mol Cancer Ther 2009;8:2402-11.
91. Hadaschik BA, Jackson J, Fazli L, Zoubeidi A, Burt HM, Gleave ME et al. Intravesically administered antisense oligonucleotides targeting heat-shock protein-27 inhibit the growth of non-muscle-invasive bladder cancer. BJU Int 2008;102:610-6.
92. Zhao Y, Li Y, Wang Q, Wang L, Yang H, Li M. Increased antitumor capability of fiber-modified adenoviral vector armed with TRAIL against bladder cancers. Mol Cell Biochem 2011;353.93-9.
93. Sayers TJ. Targeting the extrinsic apoptosis signaling pathway for cancer therapy. Cancer Immunol Immunother 2011;60:1173-80.
94. Papageorgiou A, Kamat A, Benedict WF, Dinney C, McConkey DJ. Combination therapy with IFN-alpha plus bortezomib induces apoptosis and inhibits angiogenesis in human bladder cancer cells. Mol Cancer Ther 2006;5:3032-41. (Pubitemid 46092044)
95. Metwalli AR, Khanbolooki S, Jinesh G, Sundi D, Shah JB, Shrader M et al. Smac mimetic reverses resistance to TRAIL and chemotherapy in human urothelial cancer cells. Cancer Biol Ther 2010;10:885-92.
96. Griffith TS, Kucaba TA, O'Donnell MA, Burns J, Benetatos C, McKinlay MA et al. Sensitization of human bladder tumor cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis with a small molecule IAP antagonist. Apoptosis 2011;16:13-26.
97. Rosevear HM, Lightfoot AJ, O'Donnell MA, Griffith TS. The role of neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in bacillus Calmette-Guerin (BCG) immunotherapy for urothelial carcinoma of the bladder. Cancer Metastasis Rev 2009;28:345-53.
98. Kamat AM, Tharakan ST, Sung B, Aggarwal BB. Curcumin potentiates the antitumor effects of Bacillus Calmette-Guerin against bladder cancer through the downregulation of NF-kappaB and upregulation of TRAIL receptors. Cancer Res 2009;69:8958-66.
99. Hood L, Friend SH. Predictive, personalized, preventive, participatory (P4) cancer medicine. Nat Rev Clin Oncol 2011;8:184-7.
100. Smith SC, Baras AS, Lee JK, Theodorescu D. The COXEN principle: translating signatures of in vitro chemosensitivity into tools for clinical outcome prediction and drug discovery in cancer. Cancer Res 2010;70:1753-8.