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Targeted Oncology
Erschienen in: Targeted Oncology 3/2015

01.09.2015 | Review

The route to personalized medicine in bladder cancer: where do we stand?

verfasst von: Francesco Massari, Chiara Ciccarese, Matteo Santoni, Matteo Brunelli, Alessandro Conti, Alessandra Modena, Rodolfo Montironi, Daniele Santini, Liang Cheng, Guido Martignoni, Stefano Cascinu, Giampaolo Tortora

Erschienen in: Targeted Oncology | Ausgabe 3/2015

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Abstract

Recent advances in molecular biology and drug design have described novel targets in bladder cancer. EGFR, fibroblast growth factor receptor (FGFR), VEGFR, phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, PD-1, cyclooxygenase 2 (COX-2), Aurora kinase A, and miRNA are just examples of these opening frontiers. In addition, epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs) are promising candidates for future therapeutic approaches. Novel agents, combination, and sequences are emerging from the 747 clinical studies presently in course in bladder cancer to optimize patient outcomes. This report describes the emerging targets and provides an update on ongoing phase I, II, and III trials and preliminary results on targeted agents, used alone, in sequences, or in combination for patients with bladder cancer.
Literatur
1.
Wu XR (2005) Urothelial tumorigenesis: a tale of divergent pathways. Nat Rev Cancer 5:713–725PubMedCrossRef
2.
Stoehr R, Zietz S, Burger M, Filbeck T, Denzinger S et al (2005) Deletions of chromosomes 9 and 8p in histologically normal urothelium of patients with bladder cancer. Eur Urol 47:58–63PubMedCrossRef
3.
Iyer G, Al-Ahmadie H, Schultz N, Hanrahan AJ, Ostrovnaya I et al (2013) Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer. J Clin Oncol 31:3133–3140PubMedCentralPubMedCrossRef
4.
AIOM - AIRTUM (2013) I numeri del cancro in Italia 2013. 1st ed. pp 15 - 25. Intermedia Editor: Brescia
5.
Bellmunt J, de Wit R, Albiol S, Tabernero J, Albanell J et al (2003) New drugs and new approaches in metastatic bladder cancer. Crit Rev Oncol Hemathol 47:195–206CrossRef
6.
Lipponen P, Eskelinen M (1994) Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis. Br J Cancer 69:1120–1125PubMedCentralPubMedCrossRef
7.
Pusztai L, Lewis CE, Lorenzen J, McGee JO (1993) Growth factors: regulation of normal and neoplastic growth. J Pathol 169:191–201PubMedCrossRef
8.
Bellmunt J, Hussain M, Dinney CP (2003) Novel approaches with targeted therapies in bladder cancer therapy of bladder cancer by blockade of the epidermal growth factor receptor family. Crit Rev Oncol Hematol 46:S85–S104PubMedCrossRef
9.
10.
Kim WT, Kim J, Yan C, Jeong P, Choi SY et al (2014) S100A9 and EGFR gene signatures predict disease progression in muscle invasive bladder cancer patients after chemotherapy. Ann Oncol 25(5):974–979PubMedCrossRef
11.
Hsieh TF, Chen CC, Ma WL, Chuang WM, Hung XF et al (2013) Epidermal growth factor enhances androgen receptor-mediated bladder cancer progression and invasion via potentiation of AR transactivation. Oncol Rep 30(6):2917–2922PubMed
12.
Bellmunt J, Teh BT, Tortora G, Rosenberg JE (2013) Molecular targets on the horizon for kidney and urothelial cancer. Nat Rev Clin Oncol 10:557–570PubMedCrossRef
13.
McConkey DJ, Choi W, Marquis L, Martin F, Williams MB et al (2009) Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev 28(3–4):335–344PubMedCrossRef
14.
Adam L, Zhong M, Choi W, Qi W, Nicoloso M et al (2009) miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy. Clin Cancer Res 15:5060–5072PubMedCrossRef
15.
Rebouissou S, Bernard-Pierrot I, de Reyniès A, Lepage ML, Krucker C et al (2014) EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype. Sci Transl Med 6:244ra91PubMedCrossRef
16.
Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A et al (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 230:1132–1139PubMedCrossRef
17.
Sato K, Moriyama M, Mori S, Saito M, Watanuki T et al (1992) An immunohistologic evaluation of C-erbB-2 gene product in patients with urinary bladder carcinoma. Cancer 70:2493–2498PubMedCrossRef
18.
Gandour-Edwards R, Lara PN Jr, Folkins AK, LaSalle JM, Beckett L et al (2002) Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma? Cancer 95:1009–1015PubMedCrossRef
19.
Wester K, Sjöström A, de la Torre M, Carlsson J, Malmström PU (2002) HER-2: a possible target for therapy of metastatic urinary bladder carcinoma. Acta Oncol 41:282–288PubMedCrossRef
20.
Coogan CL, Estrada CR, Kapur S, Bloom KJ (2004) HER-2/neu protein overexpression and gene amplification in human transitional cell carcinoma of the bladder. Urology 63:786–790PubMedCrossRef
21.
Laé M, Couturier J, Oudard S, Radvanyi F, Beuzeboc P et al (2010) 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 21:815–819PubMedCentralPubMedCrossRef
22.
Krüger S, Weitsch G, Büttner H, Matthiensen A, Böhmer T et al (2002) Overexpression of c-erbB-2 oncoprotein in muscle-invasive bladder carcinoma: relationship with gene amplification, clinicopathological parameters and prognostic outcome. Int J Oncol 21:981–987PubMed
23.
Miyamoto H, Kubota Y, Noguchi S, Takase K, Matsuzaki J et al (2000) C-ERBB-2 gene amplification as a prognostic marker in human bladder cancer. Urology 55:679–683PubMedCrossRef
24.
Fleischmann A, Rotzer D, Seiler R, Studer UE, Thalmann GN (2011) Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours. Eur Urol 60:350–357PubMedCrossRef
25.
Sauter G, Moch H, Moore D, Carroll P, Kerschmann R et al (1993) Heterogeneity of erbB-2 gene amplification in bladder cancer. Cancer Res 53:2199–2203PubMed
26.
Lonn U, Lönn S, Friberg S, Nilsson B, Silfverswärd C et al (1995) Prognostic value of amplification of c-erb-B2 in bladder carcinoma. Clin Cancer Res 1:1189–1194PubMed
27.
Jimenez RE, Hussain M, Bianco FJ Jr, Vaishampayan U, Tabazcka P et al (2001) 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 7:2440–2447PubMed
28.
Hussain MH, MacVicar GR, Petrylak DP, Dunn RL, Vaishampayan U et al (2007) 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 25:2218–2224PubMedCrossRef
29.
Beuzeboc P et al (2007) Trastuzumab (T) combined with standard chemotherapy in HER+ metastatic bladder cancer (BC) patients: interim safety results of a prospective randomized phase II study (abstract). J Clin Oncol 25(Suppl):a15565
30.
Wülfing C, Machiels JP, Richel DJ, Grimm MO, Treiber U et al (2009) 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 115:2881–2890PubMedCrossRef
31.
Becker MN, Wu KJ, Marlow LA, Kreinest PA, Vonroemeling CA et al (2014) The combination of an mTORc1/TORc2 inhibitor with lapatinib is synergistic in bladder cancer in vitro. Urol Oncol 32(3):317–326PubMedCrossRefPubMedCentral
32.
Böttcher RT, Niehrs C (2005) Fibroblast growth factor signalling during early vertebrate development. Endocr Rev 26(1):63–77PubMedCrossRef
33.
34.
35.
Tomlinson DC, Baldo O, Harnden P, Knowles MA (2007) FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer. J Pathol 213(1):91–98PubMedCentralPubMedCrossRef
36.
Cappellen D, De Oliveira C, Ricol D, de Medina S, Bourdin J et al (1999) Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet 23(1):18–20PubMedCrossRef
37.
van Rhijn BW, Lurkin I, Radvanyi F, Kirkels WJ, van der Kwast TH et al (2001) The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer Res 61(4):1265–1268PubMed
38.
Tomlinson DC, Knowles MA (2010) Altered splicing of FGFR1 is associated with high tumour grade and stage and leads to increased sensitivity to FGF1 in bladder cancer. Am J Pathol 177(5):2379–2386PubMedCentralPubMedCrossRef
39.
van Rhijn BW, van der Kwast TH, Vis AN, Kirkels WJ, Boevé ER et al (2004) FGFR3 and P53 characterize alternative genetic pathways in the pathogenesis of urothelial cell carcinoma. Cancer Res 64:1911–1914PubMedCrossRef
40.
Burger M, van der Aa MN, van Oers JM, Brinkmann A, van der Kwast TH et al (2008) 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 54(4):835–843PubMedCrossRef
41.
Kompier LC, van der Aa MN, Lurkin I, Vermeij M, Kirkels WJ et al (2009) The development of multiple bladder tumour recurrences in relation to the FGFR3 mutation status of the primary tumour. J Pathol 218:104–112PubMedCrossRef
42.
van Rhijn BW, van der Kwast TH, Liu L, Fleshner NE, Bostrom PJ et al (2012) The FGFR3 mutation is related to favorable pT1 bladder cancer. J Urol 187(1):310–314PubMed
43.
van Oers JM, Zwarthoff EC, Rehman I, Azzouzi AR, Cussenot O et al (2009) FGFR3 mutations indicate better survival in invasive upper urinary tract and bladder tumours. Eur Urol 55(3):650–657PubMedCrossRef
44.
Tomlinson DC, Lamont FR, Shnyder SD, Knowles MA (2009) Fibroblast growth factor receptor 1 promotes proliferation and survival via activation of the mitogen-activated protein kinase pathway in bladder cancer. Cancer Res 69(11):4613–4620PubMedCentralPubMedCrossRef
45.
Das K, Zhao Y, Sugiono M, Lau W, Tan PH et al (2007) Differential expression of vascular endothelial growth factor 165b in transitional cell carcinoma of the bladder. Urol Oncol 25(4):317–321PubMedCrossRef
46.
Ferrara N (2002) VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2:795–803PubMedCrossRef
47.
Crew JP, O'Brien T, Bradburn M, Fuggle S, Bicknell R et al (1997) Vascular endothelial growth factor is a predictor of relapse and stage progression in superficial bladder cancer. Cancer Res 57:5281–5285PubMed
48.
Inoue K, Slaton JW, Karashima T, Yoshikawa C, Shuin T et al (2000) The prognostic value of angiogenesis factor expression for predicting recurrence and metastasis of bladder cancer after neoadjuvant chemotherapy and radical cystectomy. Clin Cancer Res 6:4866–4873PubMed
49.
Yang CC, Chu KC, Yeh WM (2004) The expression of vascular endothelial growth factor in transitional cell carcinoma of urinary bladder is correlated with cancer progression. Urol Oncol 22:1–6PubMedCrossRef
50.
Donmez G, Sullu Y, Baris S, Yildiz L, Aydin O et al (2009) Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and trombospondin-1 (TSP-1) expression in urothelial carcinomas. Pathol Res Pract 205:854–857PubMedCrossRef
51.
Urquidi V, Goodison S, Kim J, Chang M, Dai Y et al (2012) Vascular endothelial growth factor, carbonic anhydrase 9, and angiogenin as urinary biomarkers for bladder cancer detection. Urology 79(5):1185.e1-6PubMedCrossRef
52.
Crew JP, O'Brien T, Bicknell R, Fuggle S, Cranston D et al (1999) Urinary vascular endothelial growth factor and its correlation with bladder cancer recurrence rates. J Urol 161(3):799–804PubMedCrossRef
53.
Eissa S, Salem AM, Zohny SF, Hegazy MG (2007) The diagnostic efficacy of urinaryy TGF-beta1 and VEGF in bladder cancer: comparison with voided urine cytology. Cancer Biomark 3(6):275–285PubMed
54.
Jeon SH, Lee SJ, Chang SG (2001) Clinical significance of urinary vascular endothelial growth factor in patients with superficial bladder tumors. Oncol Rep 8(6):1265–1267PubMed
55.
Hahn NM, Stadler WM, Zon RT, Waterhouse D, Picus J et al (2011) Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma: Hoosier Oncology Group GU 04-75. J Clin Oncol 29(12):1525–1530PubMedCrossRef
56.
Kopparapu PK, Boorjian SA, Robinson BD, Downes M, Gudas LJ et al (2013) Expression of VEGF and its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer. Anticancer Res 33:2381–2390PubMed
57.
Xia G, Kumar SR, Hawes D, Cai J, Hassanieh L et al (2006) Expression and significance of vascular endothelial growth factor receptor 2 in bladder cancer. J Urol 175(4):1245–1252PubMedCrossRef
58.
Grivas PD, Daignault S, Tagawa ST, Nanus DM, Stadler WM et al (2014) Double-blind, randomized, phase 2 trial of maintenance sunitinib versus placebo after response to chemotherapy in patients with advanced urothelial carcinoma. Cancer 120(5):692–701PubMedCrossRef
59.
Galsky MD, Hahn NM, Powles T, Hellerstedt BA, Lerner SP et al (2013) Gemcitabine, cisplatin, and sunitinib for metastatic urothelial carcinoma and as preoperative therapy for muscle-invasive bladder cancer. Clin Genitourin Cancer 11(2):175–181PubMedCrossRef
60.
Gallagher DJ, Milowsky MI, Gerst SR, Ishill N, Riches J et al (2010) Phase II study of sunitinib in patients with metastatic urothelial cancer. J Clin Oncol 28(8):1373–1379PubMedCrossRef
61.
Dreicer R, Li H, Stein M, DiPaola R, Eleff M et al (2009) Phase 2 trial of sorafenib in patients with advanced urothelial cancer: a trial of the Eastern Cooperative Oncology Group. Cancer 115(18):4090–4095PubMedCentralPubMedCrossRef
62.
Sridhar SS, Winquist E, Eisen A, Hotte SJ, McWhirter E et al (2011) A phase II trial of sorafenib in first-line metastatic urothelial cancer: a study of the PMH Phase II Consortium. Invest New Drugs 29(5):1045–1049PubMedCrossRef
63.
Pili R, Qin R, Flynn PJ, Picus J, Millward M et al (2013) A phase II safety and efficacy study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor pazopanib in patients with metastatic urothelial cancer. Clin Genitourin Cancer 11(4):477–483PubMedCentralPubMedCrossRef
64.
Santoni M, Amantini C, Morelli MB, Liberati S, Farfariello V et al (2013) Pazopanib and sunitinib trigger autophagic and non-autophagic death of bladder tumour cells. Br J Cancer 109(4):1040–1050PubMedCentralPubMedCrossRef
65.
Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC et al (1996) Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87(7):1171–1180PubMedCrossRef
66.
Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ et al (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277(5322):55–60PubMedCrossRef
67.
Oka N, Yamamoto Y, Takahashi M, Nishitani M, Kanayama HO et al (2005) Expression of angiopoietin-1 and -2, and its clinical significance in human bladder cancer. BJU Int 95(4):660–663PubMedCrossRef
68.
Quentin T, Schlott T, Korabiowska M, Käthei N, Zöller G et al (2004) Alteration of the vascular endothelial growth factor and angiopoietins-1 and -2 pathways in transitional cell carcinomas of the urinary bladder associated with tumor progression. Anticancer Res 24:2745–2756PubMed
69.
Szarvas T, Jäger T, Tötsch M, vom DF, Kempkensteffen C, et al. (2008) Angiogenic swich of angiopoietinns-Tie2 system and its prognostic value in bladder cancer. Clin Cancer Res 14:8253–8262
70.
71.
Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer 2(7):489–501PubMedCrossRef
72.
Luo J, Manning BD, Cantley LC (2003) Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 4:257–262PubMedCrossRef
73.
Ross RL, Askham JM, Knowles MA (2013) PIK3CA mutation spectrum in urothelial carcinoma reflects cell context-dependent signaling and phenotypic outputs. Oncogene 32:768–776PubMedCrossRef
74.
75.
Milowsky MI, Iyer G, Regazzi AM, Al-Ahmadie H, Gerst SR et al (2013) Phase II study of everolimus in metastatic urothelial cancer. BJU Int 112:462–470PubMedCentralPubMedCrossRef
76.
77.
Storm SM, Cleveland JL, Rapp UR (1990) Expression of raf family proto-oncogenes in normal mouse tissues. Oncogene 5:345–351PubMed
78.
79.
Chong H, Vikis HG, Guan KL (2003) Mechanisms of regulating the Raf kinase family. Cell Signal 15:463–469PubMedCrossRef
80.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S et al (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–954PubMedCrossRef
81.
Cohen Y, Xing M, Mambo E, Guo Z, Wu G et al (2003) BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst 95:625–627PubMedCrossRef
82.
Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA (2003) High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 63:1454–1457PubMed
83.
Hertzman Johansson C, Egyhazi Brage S (2014) BRAF inhibitors in cancer therapy. Pharmacol Ther 142:176–182PubMedCrossRef
84.
Karlou M, Saetta AA, Korkolopoulou P, Levidou G, Papanastasiou P, Boltetsou E, Isaiadis D, Pavlopoulos P, Thymara I, Thomas-Tsagli E, Patsouris E (2009) Activation of extracellular regulated kinases (ERK1/2) predicts poor prognosis in urothelial bladder carcinoma and is not associated with B-Raf gene mutations. Pathology 41:327–334PubMedCrossRef
85.
Zaravinos A, Chatziioannou M, Lambrou GI, Boulalas I, Delakas D, Spandidos DA (2011) Implication of RAF and RKIP genes in urinary bladder cancer. Pathol Oncol Res 17:181–190PubMedCrossRef
86.
Boulalas I, Zaravinos A, Karyotis I, Delakas D, Spandidos DA (2009) Activation of RAS family genes in urothelial carcinoma. J Urol 181:2312–2319PubMedCrossRef
87.
Mhawech-Fauceglia P, Fischer G, Beck A, Cheney RT, Herrmann FR (2006) Raf1, Aurora-A/STK15 and E-cadherin biomarkers expression in patients with pTa/pT1 urothelial bladder carcinoma; a retrospective TMA study of 246 patients with long-term follow-up. Eur J Surg Oncol 32:439–444PubMedCrossRef
88.
Simon R, Richter J, Wagner U, Fijan A, Bruderer J et al (2001) High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer. Cancer Res 61:4514–4519PubMed
89.
de Martino M, Shariat SF, Hofbauer SL, Lucca I, Taus C, et al. (2014) Aurora A kinase as a diagnostic urinary marker for urothelial bladder cancer. World J Urol
90.
Zhou N, Singh K, Mir MC, Parker Y, Lindner D et al (2013) The investigational Aurora kinase A inhibitor MLN8237 induces defects in cell viability and cell-cycle progression in malignant bladder cancer cells in vitro and in vivo. Clin Cancer Res 19(7):1717–1728PubMedCentralPubMedCrossRef
91.
Kamada M, So A, Muramaki M, Rocchi P, Beraldi E et al (2007) Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells. Mol Cancer Ther 6(1):299–308PubMedCrossRef
92.
Garg M, Kanojia D, Seth A, Kumar R, Gupta A et al (2010) Heat-shock protein 70-2 (HSP70-2) expression in bladder urothelial carcinoma is associates with tumour progression and promotes migration and invasion. Eur J Cancer 46(1):207–215PubMedCrossRef
93.
Lebret T, Watson RW, Molinié V, O’Neill A, Gabriel C et al (2003) Heat shock proteins HSP27, HSP60, HSP70, and HSP90: expression in bladder carcinoma. Cancer 98:970–977PubMedCrossRef
94.
Ma L, Sato F, Sato R, Matsubara T, Hirai K et al (2014) Dual targeting of heat shock proteins 90 and 70 promotes cell death and enhances the anticancer effect of chemotherapeutic agents in bladder cancer. Oncol Rep 31(6):2482–2492PubMedCentralPubMed
95.
Kawai T, Enomoto Y, Morikawa T, Matsushita H, Kume H et al (2014) High expression of heat shock protein 105 predicts a favorable prognosis for patients with urinary bladder cancer treated with radical cystectomy. Mol Clin Oncol 2:38–42PubMedCentralPubMed
96.
Cheng L, Davison DD, Adams J, Lopez-Beltran A, Wang L et al (2014) Biomarkers in bladder cancer: translational and clinical implications. Crit Rev Oncol Hematol 89(1):73–111PubMedCrossRef
97.
Shimada K, Anai S, Marco DA, Fujimoto K, Konishi N (2011) Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2α contributes to human bladder cancer cell survival. BMC Urol 11:8PubMedCentralPubMedCrossRef
98.
Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y et al (2014) MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515:558–562PubMedCrossRef
99.
Calin GA (2006) MicroRNA signatures in human cancers. Nat Rev 6:857–866CrossRef
100.
Zabolotneva AA, Zhavoronkov A, Garazha AV, Roumiantsev SA, Buzdin AA (2013) Characteristic patterns of microRNA expression in human bladder cancer. Front Genet 3(310):1–5
101.
Pignot G, Cizeron-Clairac G, Vacher S, Susini A, Tozlu S et al (2013) microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer. Int J Cancer 132(11):2479–2491PubMedCrossRef
102.
Catto JW, Miah S, Owen HC, Bryant H, Myers K et al (2009) Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Res 69(21):8472–8481PubMedCentralPubMedCrossRef
103.
Peinado H, Olmeda D, Cano A (2007) Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7(6):415–428PubMedCrossRef
104.
McConkey DJ, Choi W, Marquis L, Martin F, Williams MB et al (2009) Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev 28:335–344PubMedCrossRef
105.
Rieger-Christ KM, Ng L, Hanley RS, Durrani O, Ma H et al (2005) Restoration of plakoglobin expression in bladder carcinoma cell lines suppresses cell migration and tumorigenic potential. Br J Cancer 92:2153–2159PubMedCentralPubMedCrossRef
106.
Gee J et al (1998) Aberrant cadherin expression in bladder carcinoma cells. Mol Urol 2:73–81
107.
108.
Jing Y, Cui D, Guo W, Jiang J, Jiang B et al (2014) Activated androgen receptor promotes bladder cancer metastasis via Slug mediated epithelial-mesenchymal transition. Cancer Lett 348(1–2):135–145PubMedCrossRef
109.
Hänze J, Henrici M, Hegele A, Hofmann R, Olbert PJ (2013) Epithelial mesenchymal transition status is associated with anti-cancer responses towards receptor tyrosine-kinase inhibition by dovitinib in human bladder cancer cells. BMC Cancer 13:589PubMedCentralPubMedCrossRef
110.
Baumgart E, Cohen MS, Silva Neto B, Jacobs MA, Wotkowicz C et al (2007) Identification and prognostic significance of an epithelial-mesenchymal transition expression profile in human bladder tumors. Clin Cancer Res 13:1685–1694PubMedCrossRef
111.
Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5:275–284PubMedCrossRef
112.
Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW et al (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1:313–323PubMedCrossRef
113.
Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737PubMedCrossRef
114.
115.
Takebe N, Harris PJ, Warren RQ, Ivy SP (2011) Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol 8(2):97–106PubMedCrossRef
116.
Shin K, Lee J, Guo N, Kim J, Lim A et al (2011) Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder. Nature 472:110–114PubMedCentralPubMedCrossRef
117.
118.
van Tilborg AA, de Vries A, de Bont M, Groenfeld LE, van der Kwast TH et al (2000) Molecular evolution of multiple recurrent cancers of the bladder. Hum Mol Genet 9:2973–2980PubMedCrossRef
119.
120.
Kompier LC, van der Aa MN, Lurkin I, Vermeij M, Kirkels WJ et al (2009) The development of multiple bladder tumour recurrences in relation to the FGFR3 mutation status of the primary tumour. J Pathol 218:104–112PubMedCrossRef
Metadaten
Titel
The route to personalized medicine in bladder cancer: where do we stand?
verfasst von
Francesco Massari
Chiara Ciccarese
Matteo Santoni
Matteo Brunelli
Alessandro Conti
Alessandra Modena
Rodolfo Montironi
Daniele Santini
Liang Cheng
Guido Martignoni
Stefano Cascinu
Giampaolo Tortora
Publikationsdatum
01.09.2015
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 3/2015
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-015-0357-x

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Comparison of tyrosine kinase receptors HER2, EGFR, and VEGFR expression in micropapillary urothelial carcinoma with invasive urothelial carcinoma

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

23.04.2024 Medikamente in Schwangerschaft und Stillzeit Nachrichten

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

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