Prospects for precision therapy of bladder urothelial carcinoma

References

• Malats N, Real FX. Epidemiology of bladder cancer. Hematol Oncol Clin North Am. 2015;29(2):177–189.
   PubMed Web of Science ®Google Scholar
• Antoni S, Ferlay J, Soerjomataram I, et al. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol. 2017;71(1):96–108.
   PubMed Web of Science ®Google Scholar
• American Cancer Society. Cancer facts & figures. 2016. DOI:10.1101/gad.1593107
   Google Scholar
• U.S. Food and Drug Administration. Paving the way for personalized medicine paving the way for personalized medicine. Per Med. 2013;5–11.
   Google Scholar
• Abida W, Bajorin DF, Rosenberg JE. First-line treatment and prognostic factors of metastatic bladder cancer for platinum-eligible patients. Hematol Oncol Clin North Am. 2015;29(2):319–328.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Rose TL, Milowsky MI. Improving systemic chemotherapy for bladder cancer. Curr Oncol Rep. 2016;18(5):27.
   PubMed Web of Science ®Google Scholar
• Bellmunt J, von der Maase H, Mead GM, et al. Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC intergroup study 30987. J Clin Oncol. 2012;30(10):1107–1113.
   PubMed Web of Science ®Google Scholar
• Funt SA, Rosenberg JE. Systemic, perioperative management of muscle-invasive bladder cancer and future horizons. Nat Rev Clin Oncol. 2017;14(4):221–234.
   PubMed Web of Science ®Google Scholar
• Hussain S, Palmer DH, Lloyd B, et al. A study of split-dose cisplatin-based neo-adjuvant chemotherapy in muscle-invasive bladder cancer. Oncol Lett. 2012;3(4):855–859.
   PubMed Web of Science ®Google Scholar
• Necchi A, Pintarelli G, Raggi D, et al. Association of an aurora kinase a (AURKA) gene polymorphism with progression-free survival in patients with advanced urothelial carcinoma treated with the selective aurora kinase a inhibitor alisertib. Invest New Drugs. 2017;35(4):524–528.
   PubMed Web of Science ®Google Scholar
• Oing C, Rink M, Oechsle K, et al. Second line chemotherapy for advanced and metastatic urothelial carcinoma: vinflunine and beyond – a comprehensive review of the current literature. J Urol. 2016;195(2):254–263.
   PubMed Web of Science ®Google Scholar
• Raggi D, Miceli R, Sonpavde G, et al. Second-line single-agent versus doublet chemotherapy as salvage therapy for metastatic urothelial cancer: a systematic review and meta-analysis. Ann Oncol. 2016;27(1):49–61.
   PubMed Web of Science ®Google Scholar
• Bellmunt J, Théodore 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.
   PubMed Web of Science ®Google Scholar
• Bellmunt J, Fougeray R, Rosenberg JE, et al. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy. Ann Oncol. 2013;24(6):1466–1472.
   PubMed Web of Science ®Google Scholar
• Holmsten K, Hammer Dohn L, Jensen N, et al. Vinflunine treatment in patients with metastatic urothelial cancer: a Nordic retrospective multicenter analysis. Oncol Lett. 2016;12(2):1293–1300.
   PubMed Web of Science ®Google Scholar
• Pistamaltzian N, Tzannis K, Pissanidou V, et al. Treatment of relapsed urothelial bladder cancer with vinflunine. Anticancer Drugs. 2016;27(1):48–53.
   PubMed Web of Science ®Google Scholar
• Retz M, de Geeter P, Goebell PJ, et al. Vinflunine in routine clinical practice for the treatment of advanced or metastatic urothelial cell carcinoma – data from a prospective, multicenter experience. BMC Cancer. 2015;15(1):455.
   PubMed Web of Science ®Google Scholar
• Kamat AM, Hahn NM, Efstathiou JA, et al. Seminar bladder cancer. Lancet. 2016;6736(16):1–15.
   Google Scholar
• Ciccarese C, Massari F, Blanca A, et al. Tp53 and its potential therapeutic role as a target in bladder cancer. Expert Opin Ther Targets. 2017;21(4):401–414.
   PubMed Web of Science ®Google Scholar
• Van Allen EM, Mouw KW, Kim P, et al. Somatic ERCC2 mutations correlate withcisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov. 2014;4(10):1140–1153.
   PubMed Web of Science ®Google Scholar
• Plimack ER, Dunbrack RL, Brennan TA, et al. Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Eur Urol. 2015;68(6):959–967.
   PubMed Web of Science ®Google Scholar
• Teo MY, Bambury R, Zabor EC, et al. DNA damage response and repair gene alterations are associated with improved survival in patients with platinum-treated advanced urothelial carcinoma. Clin Cancer Res. 2017 Jan 30;23(14):3610–3618. DOI:10.1158/1078-0432.CCR-16-2520
   PubMed Web of Science ®Google Scholar
• O’Donnell PH, Alanee S, Stratton KL, et al. Clinical evaluation of cisplatin sensitivity of germline polymorphisms in neoadjuvant chemotherapy for urothelial cancer. Clin Genitourin Cancer. 2016;14(6):511–517.
   PubMed Web of Science ®Google Scholar
• Nandagopal L, Sonpavde G. Circulating biomarkers in bladder cancer. Bladder Cancer. 2016;2(4):369–379.
   PubMed Web of Science ®Google Scholar
• Gorin MA, Verdone JE, van der Toom E, et al. Circulating tumour cells as biomarkers of prostate, bladder, and kidney cancer. Nat Rev Urol. 2017;14(2):90–97.
   PubMed Web of Science ®Google Scholar
• Boussiotis VA. Molecular and biochemical aspects of the PD-1 checkpoint pathway. New Engl J Med. 2016;375(18):1767–1778.
   PubMed Web of Science ®Google Scholar
• Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515(7528):558–562.
   PubMed Web of Science ®Google Scholar
• Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387(10031):1909–1920.
   PubMed Web of Science ®Google Scholar
• Balar AV, Apolo AB, Ostrovnaya I, et al. Phase II study of gemcitabine, carboplatin, and bevacizumab in patients with advanced unresectable or metastatic urothelial cancer. J Clin Oncol. 2013;31(6):724–730.
   PubMed Web of Science ®Google Scholar
• Plimack ER, Bellmunt J, Gupta S. Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): a nonrandomised, open-label, phase 1b study. Lancet Oncol. 2017;2045(17):1–8.
   Google Scholar
• Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. Engl J Med. 2017 Mar 16;376(11):1015–1026.
   PubMed Web of Science ®Google Scholar
• Sharma P, Callahan MK, Bono P, et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol. 2016;17(11):1590–1598.
   PubMed Web of Science ®Google Scholar
• Sharma P, Retz M, Sie A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18(3):312–322.
   PubMed Web of Science ®Google Scholar
• Bellmunt J, Powles T, Vogelzang NJ. A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: the future is now. Cancer Treat Rev. 2017;54:58–67.
   PubMed Web of Science ®Google Scholar
• Massard C, Gordon MS, Sharma S, et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol. 2016;10;34(26):3119–3125.
   Web of Science ®Google Scholar
• Vandeveer AJ, Fallon JK, Tighe R, et al. Systemic immunotherapy of non-muscle invasive mouse bladder cancer with avelumab, an anti-PD-L1 immune checkpoint inhibitor. Cancer Immunol Res. 2016;4(5):452–462.
   PubMed Web of Science ®Google Scholar
• Choudhury NJ, Campanile A, Antic T, et al. Afatinib activity in platinum-refractory metastatic urothelial carcinoma in patients with ERBB alterations. J Clin Oncol. 2016 Jun 20;34(18):2165–2171. Epub 2016 Apr 4. DOI:10.1200/JCO.2015.66.3047
   PubMed Web of Science ®Google Scholar
• Gibney GT, Weiner LM, Atkins MB. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol. 2016;17(12):e542–e551.
   PubMed Web of Science ®Google Scholar
• Bianconi M, Faloppi L, Lopez-Beltran A, et al. Immunotherapy in genitourinary cancers: where are we going? Expert Rev Precis Med Drug Dev. 2017;2(2):73–78.
   Web of Science ®Google Scholar
• Balar AV, Galsky MD, Rosenberg JE, et al.; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67–76.
   PubMed Web of Science ®Google Scholar
• Galsky MD, Hahn NM, Powles T, et al. Gemcitabine, cisplatin, and sunitinib for metastatic urothelial carcinoma and as preoperative therapy for muscle-invasive bladder cancer. Clini Genitour Cancer. 2013;11(2):175–181.
   PubMed Web of Science ®Google Scholar
• Iyer G, Al-Ahmadie H, Schultz N, et al. Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer. J Clin Oncol. 2013;31(25):3133–3140.
   PubMed Web of Science ®Google Scholar
• Roskoski R Jr. The ErbB/HER family of protein – tyrosine kinases and cancer. Pharmacol Res. 2014;79:34–74.
   PubMed Web of Science ®Google Scholar
• Miller K, Morant R, Stenzl A, et al. A phase II study of the Central European Society of Anticancer-Drug Research (CESAR) group: results of an open-label study of gemcitabine plus cisplatin with or without concomitant or sequential gefitinib in patients with advanced or metastatic transition. Urol Int. 2016;96(1):5–13.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Petrylak DP, Tangen CM, Van Veldhuizen PJ, et al. Results of the Southwest Oncology Group phase II evaluation (study S0031) of ZD1839 for advanced transitional cell carcinoma of the urothelium. BJU Int. 2010;105(3):317–321.
   PubMed Web of Science ®Google Scholar
• Jacobs MA, Wotkowicz C, Baumgart ED, et al. Epidermal growth factor receptor status and the response of bladder carcinoma cells to erlotinib. J Urol. 2007;178(4):1510–1514.
   PubMed Web of Science ®Google Scholar
• Yang J-L, Qu X-J, Hayes VM, et al. Erlotinib (OSI-774)-induced inhibition of transitional cell carcinoma of bladder cell line growth is enhanced by interferon-α. BJU Int. 2007;99(6):1539–1545.
   PubMed Web of Science ®Google Scholar
• Tang Y, Zhang X, Qi F, et al. Afatinib inhibits proliferation and invasion and promotes apoptosis of the T24 bladder cancer cell line. Exp Ther Med. 2015 May;9(5):1851–1856.
   PubMed Web of Science ®Google Scholar
• Tsai Y-C, Ho P-Y, Tzen K-Y, et al. Synergistic blockade of EGFR and HER2 by newgeneration EGFR tyrosine kinase inhibitor enhances radiation effect in bladder cancer cells. Molec Cancer Ther. 2015;14(3):810–820.
   PubMed Web of Science ®Google Scholar
• Wong Y-N, Litwin S, Vaughn D, et al. Phase II trial of cetuximab with or without paclitaxel in patients with advanced urothelial tract carcinoma. J Clin Oncol. 2012;30(28):3545–3551.
   PubMed Web of Science ®Google Scholar
• Hussain M, Daignault S, Agarwal N, et al. A randomized phase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma. Cancer. 2014;120(17):2684–2693.
   PubMed Web of Science ®Google Scholar
• Fiorentino M, Giunchi F, Altimari A, et al. Learning from errors: response to gefitinib in kidney urothelial carcinoma with EGFR mutations. Oncologist. 2014;19(4):430–430.
   PubMed Web of Science ®Google Scholar
• Hussain MHA, 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.
   PubMed Web of Science ®Google Scholar
• Massari F, Ciccarese C, Santoni M, et al. The route to personalized medicine in bladder cancer: where do we stand? Target Oncol. 2015;10(3):325–336.
   PubMed Web of Science ®Google Scholar
• Peyromaure M, Scotte F, Amsellemouazana D, et al. Trastuzumab (HerceptinTM) in metastatic transitional cell carcinoma of the urinary tract: report on six patients. Eur Urol. 2005;48(5):771–778.
   PubMed Web of Science ®Google Scholar
• Salzberg M, Borner M, Bauer J-A, et al. Trastuzumab (Herceptin®) in patients with HER-2-overexpressing metastatic or locally advanced transitional cell carcinoma of the bladder: report on 7 patients. Eur J Cancer. 2006;42(15):2660–2661.
   PubMed Web of Science ®Google Scholar
• Wezel F, Erben P, Gaiser T, et al. Complete and durable remission of human epidermal growth factor receptor 2-positive metastatic urothelial carcinoma following third-line treatment with trastuzumab and gemcitabine. Urol Int. 2016. DOI:10.1159/000443280
   PubMedGoogle Scholar
• Oudard S, Culine S, Vano Y, et al. Multicentre randomised phase II trial of gemcitabine+platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2. Eur J Cancer. 2015;51(1):45–54.
   PubMed Web of Science ®Google Scholar
• Narayan V, Mamtani R, Keefe S, et al. Cisplatin, gemcitabine, and lapatinib as neoadjuvant therapy for muscle-invasive bladder cancer. Cancer Res Treat. 2016;48(3):1084–1091.
   PubMed Web of Science ®Google Scholar
• Wülfing C, Machiels JPH, 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.
   PubMed Web of Science ®Google Scholar
• Culine S, Sellam Z, Bouaita L, et al. Combining paclitaxel and lapatinib as second-line treatment for patients with metastatic transitional cell carcinoma: a case series. Anticancer Res. 2012;32(9):3949–3952.
   PubMed Web of Science ®Google Scholar
• Frampton GM, Fichtenholtz A, Otto GA, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013 Nov;31(11):1023–1031. Epub 2013 Oct 20. DOI:10.1038/nbt.2696
   PubMed Web of Science ®Google Scholar
• Milowsky MI, Dittrich C, Durán I, et al. Phase 2 trial of dovitinib in patients with progressive FGFR3-mutated or FGFR3 wild-type advanced urothelial carcinoma. Eur J Cancer. 2014;50(18):3145–3152.
   PubMed Web of Science ®Google Scholar
• Nogova L, Sequist LV, Perez Garcia JM, et al. Evaluation of BGJ398, a fibroblast growth factor receptor 1-3 kinase inhibitor, in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors: results of a global phase I, dose escalation and dose-expansion study. J Clin Oncol. 2016;35(2):157–165.
   PubMed Web of Science ®Google Scholar
• Palma N, Morris JC, Ali SM, et al. Exceptional response to pazopanib in a patient with urothelial carcinoma harboring FGFR3 activating mutation and amplification. Eur Urol. 2015;68(1):168–170.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Bellmunt J, Gonzalez-Larriba J, Prior C, 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(12):2646–2653.
   PubMed Web of Science ®Google Scholar
• Geldart T, Chester J, Casbard A, et al. SUCCINCT: an open-label, single-arm, nonrandomised, phase 2 trial of gemcitabine and cisplatin chemotherapy in combination with sunitinib as first-line treatment for patients with advanced urothelial carcinoma. Eur Urol. 2015;67(4):599–602.
   PubMed Web of Science ®Google Scholar
• Grivas PD, Daignault S, Tagawa S, et al. Double-blind, randomized, phase 2 trial of maintenance sunitinib versus placebo after response to chemotherapy in patients with advanced urothelial carcinoma. Cancer. 2014;120(5):692–701.
   PubMed Web of Science ®Google Scholar
• Narayanan S, Lam A, Vaishampayan U, et al. Phase II study of pazopanib and paclitaxel in patients with refractory urothelial cancer. Clin Genitourin Cancer. 2016;14(5):432–437.
   PubMed Web of Science ®Google Scholar
• Pili R, Qin R, Flynn PJ, et al. 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. 2013;11(4):477–483.
   PubMed Web of Science ®Google Scholar
• Pinciroli P, Won H, Iyer G, et al. Molecular signature of response to pazopanib salvage therapy for urothelial carcinoma. Clin Genitourin Cancer. 2016;14(1):e81–e90.
   PubMed Web of Science ®Google Scholar
• Necchi A, Pennati M, Zaffaroni N, et al. Analysis of plasma cytokines and angiogenic factors in patients with pretreated urothelial cancer receiving Pazopanib: the role of circulating interleukin-8 to enhance the prognostic accuracy. Br J Cancer. 2014;110(1):26–33.
   PubMed Web of Science ®Google Scholar
• Dreicer R, Li H, Stein M, et al. Phase 2 trial of sorafenib in patients with advanced urothelial cancer. Cancer. 2009;115(18):4090–4095.
   PubMed Web of Science ®Google Scholar
• Krege S, Rexer H, vom Dorp F, et al. Prospective randomized double-blind multicenter phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05). BJU Int. 2014;113(3):429–436.
   PubMed Web of Science ®Google Scholar
• Sridhar SS, Winquist E, Eisen A, et al. A phase II trial of sorafenib in first-line metastatic urothelial cancer: a study of the PMH Phase II Consortium. Invest New Drugs. 2011;29(5):1045–1049.
   PubMed Web of Science ®Google Scholar
• Shintani T, Kusuhara Y, Daizumoto K, et al. The involvement of hepatocyte growth factor met matrix metalloproteinase 1 signaling in bladder cancer invasiveness and proliferation. Effect of the MET inhibitor, cabozantinib (XL184), on bladder cancer cells. Urology. 2017;101:169.e7–169.e13.
   PubMed Web of Science ®Google Scholar
• Tully CM, Apolo AB, Zabor E, et al. The high incidence of vascular thromboembolic events in patients with metastatic or unresectable urothelial cancer treated with platinum chemotherapy agents. Cancer. 2016;122(5):712–721.
   PubMed Web of Science ®Google Scholar
• Hahn NM, Stadler WM, Zon R, et al. 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. 2011;29(12):1525–1530.
   PubMed Web of Science ®Google Scholar
• Petrylak DP, Tagawa ST, Kohli M, et al. Docetaxel as monotherapy or combined with ramucirumab or icrucumab in second-line treatment for locally advanced or metastatic urothelial carcinoma: an open-label, three-arm, randomized controlled phase II trial. J Clin Oncol. 2016;34(13):1500–1509.
   PubMed Web of Science ®Google Scholar
• Moon D, Lee S, Oh M, et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor synergistically potentiates the antitumor effects of cisplatin in bladder cancer cells. Int J Oncol. 2014;45(3):1027–1035.
   PubMed Web of Science ®Google Scholar
• Fokas E, Yoshimura M, Prevo R, et al. NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity. Radiat Oncol. 2012;7(1):48.
   PubMed Web of Science ®Google Scholar
• Carlo MI, Molina AM, Lakhman Y, et al. A phase Ib study of BEZ235, a dual inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR), in patients with advanced renal cell carcinoma. Oncologist. 2016;21(7):787–788.
   PubMed Web of Science ®Google Scholar
• Fazio N, Buzzoni R, Baudin E, et al. A phase II study of BEZ235 in patients with everolimus-resistant, advanced pancreatic neuroendocrine tumours. Anticancer Res. 2016;36(2):713–719.
   PubMed Web of Science ®Google Scholar
• Iyer G, Hanrahan A, Milowsky MI, et al. Genome sequencing identifies a basis for everolimus sensitivity. Science. 2012;338(6104):221.
   PubMed Web of Science ®Google Scholar
• Milowsky MI, Iyer G, Regazzi AM, et al. Phase II study of everolimus in metastatic urothelial cancer. BJU Int. 2013;112(4):462–470.
   PubMed Web of Science ®Google Scholar
• Seront E, Rottey S, Sautois B, et al. Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers. Ann Oncol. 2012;23(10):2663–2670.
   PubMed Web of Science ®Google Scholar
• Niegisch G, Retz M, Thalgott M, et al. Second-line treatment of advanced urothelial cancer with Paclitaxel and Everolimus in a German phase II trial (AUO Trial AB 35/09). Oncology. 2015;89(2):70–78.
   PubMed Web of Science ®Google Scholar
• Abida W, Milowsky MI, Ostrovnaya I, et al. Phase I study of everolimus in combinationwith gemcitabine and split-dose cisplatin in advanced urothelial carcinoma. Bladder Cancer. 2016;2(1):111–117.
   PubMedGoogle Scholar
• Ali SM, Miller VA, Ross JS, et al. Exceptional response on addition of everolimus to taxanes in urothelial carcinoma bearing an NF2 mutation. Eur Urol. 2015;67(6):1195–1196.
   PubMed Web of Science ®Google Scholar
• Wagle N, Grabiner BC, Van Allen EM, et al. Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib. Cancer Discov. 2014;4(10):1140–1153.
   PubMed Web of Science ®Google Scholar
• Gerullis H, Eimer C, Ecke TH, et al. A phase II trial of temsirolimus in second-line metastatic urothelial cancer. Med Oncol. 2012;29(4):2870–2876.
   PubMed Web of Science ®Google Scholar
• Ji G, Qian Y. Successful treatment of metastatic upper tract urothelial carcinoma with vemurafenib: case report. Clin Genitourin Cancer. 2016. DOI:10.1016/j.clgc.2016.11.003
   PubMed Web of Science ®Google Scholar
• Zhou N, Singh K, Mir MC, et al. 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. 2013;19(7):1717–1728.
   PubMed Web of Science ®Google Scholar
• Necchi A, Lo Vullo S, Mariani L, et al. An open-label, single-arm, phase 2 study of the Aurora kinase A inhibitor alisertib in patients with advanced urothelial cancer. Invest New Drugs. 2016;34(2):236–242.
   PubMed Web of Science ®Google Scholar
• Graff JN, Higano CS, Hahn NM, et al. Open-label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors. Cancer. 2016;122(16):2524–2533.
   PubMed Web of Science ®Google Scholar
• Hadaschik BA, Jackson J, Fazli L, et al. Intravesically administered antisense oligonucleotides targeting heat-shock protein-27 inhibit the growth of non-muscleinvasive bladder cancer. BJU Int. 2008;102(5):610–616.
   PubMed Web of Science ®Google Scholar
• Kamada M, So A, Muramaki M, et al. Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells. Mol Cancer Ther. 2007;6(1):299–308.
   PubMed Web of Science ®Google Scholar
• Chi KN, Yu EY, Jacobs C, et al. A phase I dose-escalation study of apatorsen (OGX-427), an antisense inhibitor targeting heat shock protein 27 (Hsp27), in patients with castrationresistant prostate cancer and other advanced cancers. Ann Oncol. 2016;27(6):1116–1122.
   PubMed Web of Science ®Google Scholar
• Blanca A, Cheng L, Montironi R, et al. Mirna expression in bladder cancer and their potential role in clinical practice. Curr Drug Metab. 2017;18. DOI:10.2174/1389200218666170518164507
   Google Scholar
• Pan Q, Sathe A, Black PC, et al. CDK4/6 inhibitors in cancer therapy: a novel treatement strategy for bladder cancer. Bladder Cancer. 2017;3(2):79–88.
   PubMed Web of Science ®Google Scholar
• Módos O, Reis H, Niedworok C, et al. Mutations of KRAS, NRAS, BRAF, EGFR, andPIK3CA genes in urachal carcinoma – occurence and prognostic significance. Oncotarget. 2016;7(26):39293–39301.
   PubMed Web of Science ®Google Scholar