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World Journal of Urology
Published in: World Journal of Urology 1/2019

01-01-2019 | Topic Paper

SIU–ICUD consultation on bladder cancer: basic science

Authors: David J. McConkey, Seth P. Lerner

Published in: World Journal of Urology | Issue 1/2019

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Abstract

Purpose

To provide a condensed summary of the Basic Science chapter that was included in the Third International Consultation on Bladder Cancer.

Methods

World bladder cancer basic science experts used the published literature to create summaries of recent progress in their areas of expertise.

Results

The completion of several large-scale genomics projects coupled with a strong collaborative culture within the research community and the exciting clinical activity of immune checkpoint blockade have combined to transform the bladder cancer research landscape. Bladder cancer molecular subtypes and the presence of specific DNA alterations provide important information about disease heterogeneity that has direct implications for clinical management, and some can be targeted by compounds that are already clinically available. Tests are being developed that can measure many of these alterations non-invasively in peripheral blood or urine, raising confidence that they could be used as biomarkers for surveillance and monitoring the effects of local and systemic therapies.

Conclusions

Although the bulk of the mechanistic work lies ahead, the genomics results have created a hypothesis-generating description of bladder cancer heterogeneity that has set the stage for deeper mechanistic studies, and they have already provided us with extremely attractive candidate biomarkers to guide clinical practice. Here, we will summarize the recent progress in basic bladder cancer research and highlight near-term opportunities for the future.
Literature
1.
Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmstrom PU, Choi W et al (2016) Bladder cancer. Lancet 388(10061):2796–2810CrossRefPubMed
2.
Knowles MA, Hurst CD (2015) Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer 15(1):25–41CrossRefPubMed
3.
4.
Dyrskjot L, Thykjaer T, Kruhoffer M, Jensen JL, Marcussen N, Hamilton-Dutoit S et al (2003) Identifying distinct classes of bladder carcinoma using microarrays. Nat Genet 33(1):90–96CrossRefPubMed
5.
Lindgren D, Frigyesi A, Gudjonsson S, Sjodahl G, Hallden C, Chebil G et al (2010) Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome. Cancer Res 70(9):3463–3472CrossRefPubMed
6.
Sanchez-Carbayo M, Socci ND, Lozano J, Saint F, Cordon-Cardo C (2006) Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays. J Clin Oncol 24(5):778–789CrossRefPubMed
7.
Sjodahl G, Lauss M, Lovgren K, Chebil G, Gudjonsson S, Veerla S et al (2012) A molecular taxonomy for urothelial carcinoma. Clin Cancer Res 18(12):3377–3386CrossRefPubMed
8.
Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507(7492):315–322CrossRef
9.
Damrauer JS, Hoadley KA, Chism DD, Fan C, Tiganelli CJ, Wobker SE et al (2014) Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci USA 111(8):3110–3115CrossRefPubMedPubMedCentral
10.
Choi W, Porten S, Kim S, Willis D, Plimack ER, Hoffman-Censits J et al (2014) Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25(2):152–165CrossRefPubMedPubMedCentral
11.
12.
Sjodahl G, Eriksson P, Liedberg F, Hoglund M (2017) Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification. J Pathol 242(1):113–125CrossRefPubMedPubMedCentral
13.
Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, Gilcrease MZ, Krishnamurthy S, Lee JS et al (2009) Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res 69(10):4116–4124CrossRefPubMedPubMedCentral
14.
Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD et al (2017) Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell 171(3):540-56 e25CrossRef
15.
Guo CC, Dadhania V, Zhang L, Majewski T, Bondaruk J, Sykulski M et al (2016) Gene expression profile of the clinically aggressive micropapillary variant of bladder cancer. Eur Urol 70(4):611–620CrossRefPubMedPubMedCentral
16.
Warrick JI, Kaag M, Raman JD, Chan W, Tran T, Kunchala S et al (2017) FOXA1 and CK14 as markers of luminal and basal subtypes in histologic variants of bladder cancer and their associated conventional urothelial carcinoma. Virchows Arch 471(3):337–345CrossRefPubMed
17.
Hedegaard J, Lamy P, Nordentoft I, Algaba F, Hoyer S, Ulhoi BP et al (2016) Comprehensive transcriptional analysis of early-stage urothelial carcinoma. Cancer Cell 30(1):27–42CrossRefPubMed
18.
McConkey DJ, Choi W, Shen Y, Lee IL, Porten S, Matin SF et al (2016) A prognostic gene expression signature in the molecular classification of chemotherapy-naive urothelial cancer is predictive of clinical outcomes from neoadjuvant chemotherapy: a phase 2 trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with bevacizumab in urothelial cancer. Eur Urol 69(5):855–862CrossRefPubMed
19.
Seiler R, Ashab HAD, Erho N, van Rhijn BWG, Winters B, Douglas J et al (2017) Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy. Eur Urol 72(4):544–554CrossRefPubMed
20.
Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A et al (2016) 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 387(10031):1909–1920CrossRefPubMedPubMedCentral
21.
Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K, Wang Y et al (2018) TGFbeta attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 554(7693):544–548CrossRefPubMedPubMedCentral
22.
Dinney CP, Hansel D, McConkey D, Shipley W, Hagan M, Dreicer R et al (2014) Novel neoadjuvant therapy paradigms for bladder cancer: results from the National Cancer Center Institute Forum. Urol Oncol. 32(8):1108–1115CrossRefPubMedPubMedCentral
23.
Ochoa AE, Choi W, Su X, Siefker-Radtke A, Czerniak B, Dinney C et al (2016) Specific micro-RNA expression patterns distinguish the basal and luminal subtypes of muscle-invasive bladder cancer. Oncotarget. 7(49):80164–80174CrossRefPubMedPubMedCentral
24.
25.
Varley CL, Stahlschmidt J, Lee WC, Holder J, Diggle C, Selby PJ et al (2004) Role of PPARgamma and EGFR signalling in the urothelial terminal differentiation programme. J Cell Sci 117(Pt 10):2029–2036CrossRefPubMed
26.
Varley CL, Stahlschmidt J, Smith B, Stower M, Southgate J (2004) Activation of peroxisome proliferator-activated receptor-gamma reverses squamous metaplasia and induces transitional differentiation in normal human urothelial cells. Am J Pathol 164(5):1789–1798CrossRefPubMedPubMedCentral
27.
Varley CL, Bacon EJ, Holder JC, Southgate J (2009) FOXA1 and IRF-1 intermediary transcriptional regulators of PPARgamma-induced urothelial cytodifferentiation. Cell Death Differ 16(1):103–114CrossRefPubMed
28.
Biton A, Bernard-Pierrot I, Lou Y, Krucker C, Chapeaublanc E, Rubio-Perez C et al (2014) Independent component analysis uncovers the landscape of the bladder tumor transcriptome and reveals insights into luminal and basal subtypes. Cell Rep. 9(4):1235–1245CrossRefPubMed
29.
Chan KS, Espinosa I, Chao M, Wong D, Ailles L, Diehn M et al (2009) Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci USA 106(33):14016–14021CrossRefPubMedPubMedCentral
30.
He X, Marchionni L, Hansel DE, Yu W, Sood A, Yang J et al (2009) Differentiation of a highly tumorigenic basal cell compartment in urothelial carcinoma. Stem Cells. 27(7):1487–1495CrossRefPubMedPubMedCentral
31.
Yang YM, Chang JW (2008) Bladder cancer initiating cells (BCICs) are among EMA-CD44v6 + subset: novel methods for isolating undetermined cancer stem (initiating) cells. Cancer Invest 26(7):725–733CrossRefPubMed
32.
Su Y, Qiu Q, Zhang X, Jiang Z, Leng Q, Liu Z et al (2010) Aldehyde dehydrogenase 1 A1-positive cell population is enriched in tumor-initiating cells and associated with progression of bladder cancer. Cancer Epidemiol, Biomark Prevent Publ Am Assoc Cancer Res, cosponsored by the American Society of Preventive Oncology. 19(2):327–337CrossRef
33.
Volkmer JP, Sahoo D, Chin RK, Ho PL, Tang C, Kurtova AV et al (2012) Three differentiation states risk-stratify bladder cancer into distinct subtypes. Proc Natl Acad Sci USA 109(6):2078–2083CrossRefPubMedPubMedCentral
34.
Huang P, Watanabe M, Kaku H, Ueki H, Noguchi H, Sugimoto M et al (2013) Cancer stem cell-like characteristics of a CD133(+) subpopulation in the J82 human bladder cancer cell line. Mol Clin Oncol. 1(1):180–184CrossRefPubMed
35.
Cheah MT, Chen JY, Sahoo D, Contreras-Trujillo H, Volkmer AK, Scheeren FA et al (2015) CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer. Proc Natl Acad Sci USA 112(15):4725–4730CrossRefPubMedPubMedCentral
36.
Kurtova AV, Xiao J, Mo Q, Pazhanisamy S, Krasnow R, Lerner SP et al (2015) Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance. Nature 517(7533):209–213CrossRefPubMed
37.
Yang Z, Li C, Fan Z, Liu H, Zhang X, Cai Z et al (2017) Single-cell sequencing reveals variants in ARID1A, GPRC5A and MLL2 driving self-renewal of human bladder cancer stem cells. Eur Urol 71(1):8–12CrossRefPubMed
38.
Li C, Wu S, Wang H, Bi X, Yang Z, Du Y et al (2015) The C228T mutation of TERT promoter frequently occurs in bladder cancer stem cells and contributes to tumorigenesis of bladder cancer. Oncotarget. 6(23):19542–19551PubMedPubMedCentral
39.
Gui Y, Guo G, Huang Y, Hu X, Tang A, Gao S et al (2011) Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat Genet 43(9):875–878CrossRefPubMedPubMedCentral
40.
Allory Y, Beukers W, Sagrera A, Flandez M, Marques M, Marquez M et al (2014) Telomerase reverse transcriptase promoter mutations in bladder cancer: high frequency across stages, detection in urine, and lack of association with outcome. Eur Urol 65(2):360–366CrossRefPubMed
41.
Ho PL, Lay EJ, Jian W, Parra D, Chan KS (2012) Stat3 activation in urothelial stem cells leads to direct progression to invasive bladder cancer. Can Res 72(13):3135–3142CrossRef
42.
Yang Z, He L, Lin K, Zhang Y, Deng A, Liang Y et al (2017) The KMT1A-GATA3-STAT3 circuit is a novel self-renewal signaling of human bladder cancer stem cells. Clin Cancer Res 23(21):6673–6685CrossRefPubMed
43.
Shin K, Lim A, Zhao C, Sahoo D, Pan Y, Spiekerkoetter E et al (2014) Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors. Cancer Cell 26(4):521–533CrossRefPubMedPubMedCentral
44.
Chan KS (2016) Molecular pathways: targeting cancer stem cells awakened by chemotherapy to abrogate tumor repopulation. Clin Cancer Res 22(4):802–806CrossRefPubMed
45.
Venkatesan S, Rosenthal R, Kanu N, McGranahan N, Bartek J, Quezada SA et al (2018) Perspective: APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution. Ann Oncol 29(3):563–572CrossRefPubMedPubMedCentral
46.
Kim J, Mouw KW, Polak P, Braunstein LZ, Kamburov A, Kwiatkowski DJ et al (2016) Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors. Nat Genet 48(6):600–606CrossRefPubMedPubMedCentral
47.
Van Allen EM, Mouw KW, Kim P, Iyer G, Wagle N, Al-Ahmadie H et al (2014) Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov 4(10):1140–1153CrossRefPubMedPubMedCentral
48.
Li Q, Damish A, Frazier ZJ, Liu D, Reznichenko E, Kamburov A, et al (2018) ERCC2 Helicase Domain mutations confer nucleotide excision repair deficiency and drive cisplatin sensitivity in muscle-invasive bladder cancer. Clin Cancer Res
49.
Plimack ER, Dunbrack RL, Brennan TA, Andrake MD, Zhou Y, Serebriiskii IG et al (2015) Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Eur Urol 68(6):959–967CrossRefPubMedPubMedCentral
50.
Faltas BM, Prandi D, Tagawa ST, Molina AM, Nanus DM, Sternberg C et al (2016) Clonal evolution of chemotherapy-resistant urothelial carcinoma. Nat Genet 48(12):1490–1499CrossRefPubMedPubMedCentral
51.
Nordentoft I, Lamy P, Birkenkamp-Demtroder K, Shumansky K, Vang S, Hornshoj H et al (2014) Mutational context and diverse clonal development in early and late bladder cancer. Cell Rep. 7(5):1649–1663CrossRefPubMed
52.
Thomsen MBH, Nordentoft I, Lamy P, Vang S, Reinert L, Mapendano CK et al (2017) Comprehensive multiregional analysis of molecular heterogeneity in bladder cancer. Sci Rep. 7(1):11702CrossRefPubMedPubMedCentral
53.
Hurst CD, Alder O, Platt FM, Droop A, Stead LF, Burns JE et al (2017) Genomic subtypes of non-invasive bladder cancer with distinct metabolic profile and female gender bias in KDM6A mutation frequency. Cancer Cell 32(5):701–15 e7CrossRef
54.
Pietzak EJ, Bagrodia A, Cha EK, Drill EN, Iyer G, Isharwal S et al (2017) Next-generation sequencing of nonmuscle invasive bladder cancer reveals potential biomarkers and rational therapeutic targets. Eur Urol 72(6):952–959CrossRefPubMedPubMedCentral
55.
Meeks JJ, Carneiro BA, Pai SG, Oberlin DT, Rademaker A, Fedorchak K et al (2016) Genomic characterization of high-risk non-muscle invasive bladder cancer. Oncotarget. 7(46):75176–75184CrossRefPubMedPubMedCentral
56.
57.
58.
Birkenkamp-Demtroder K, Christensen E, Nordentoft I, Knudsen M, Taber A, Hoyer S et al (2018) Monitoring treatment response and metastatic relapse in advanced bladder cancer by liquid biopsy analysis. Eur Urol 73(4):535–540CrossRefPubMed
59.
Birkenkamp-Demtroder K, Nordentoft I, Christensen E, Hoyer S, Reinert T, Vang S et al (2016) Genomic alterations in liquid biopsies from patients with bladder cancer. Eur Urol 70(1):75–82CrossRefPubMed
60.
Christensen E, Birkenkamp-Demtroder K, Nordentoft I, Hoyer S, van der Keur K, van Kessel K et al (2017) Liquid biopsy analysis of FGFR3 and PIK3CA hotspot mutations for disease surveillance in bladder cancer. Eur Urol 71(6):961–969CrossRefPubMed
61.
Springer SU, Chen CH, Rodriguez Pena MDC, Li L, Douville C, Wang Y et al (2018) Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy. Elife. 7:e32143CrossRefPubMedPubMedCentral
62.
Smith E, Shilatifard A (2010) The chromatin signaling pathway: diverse mechanisms of recruitment of histone-modifying enzymes and varied biological outcomes. Mol Cell 40(5):689–701CrossRefPubMedPubMedCentral
63.
Fyodorov DV, Zhou BR, Skoultchi AI, Bai Y. Emerging roles of linker histones in regulating chromatin structure and function. Nat Rev Mol Cell Biol. 2017
64.
65.
Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD et al (2017) Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell
66.
Allis CD, Berger SL, Cote J, Dent S, Jenuwien T, Kouzarides T et al (2007) New nomenclature for chromatin-modifying enzymes. Cell 131(4):633–636CrossRefPubMed
67.
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO et al (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6(269):pl1CrossRefPubMedPubMedCentral
68.
Choi W, Ochoa A, McConkey DJ, Aine M, Hoglund M, Kim WY et al (2017) Genetic alterations in the molecular subtypes of bladder cancer: illustration in the cancer genome atlas dataset. Eur Urol 72(3):354–365CrossRefPubMedPubMedCentral
69.
Piunti A, Shilatifard A (2016) Epigenetic balance of gene expression by polycomb and COMPASS families. Science 352(6290):9780CrossRef
70.
Miller T, Krogan NJ, Dover J, Erdjument-Bromage H, Tempst P, Johnston M et al (2001) COMPASS: a complex of proteins associated with a trithorax-related SET domain protein. Proc Natl Acad Sci USA 98(23):12902–12907CrossRefPubMedPubMedCentral
71.
Ntziachristos P, Tsirigos A, Welstead GG, Trimarchi T, Bakogianni S, Xu L et al (2014) Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. Nature 514(7523):513–517CrossRefPubMedPubMedCentral
72.
Ler LD, Ghosh S, Chai X, Thike AA, Heng HL, Siew EY et al (2017) Loss of tumor suppressor KDM6A amplifies PRC2-regulated transcriptional repression in bladder cancer and can be targeted through inhibition of EZH2. Sci Transl Med 9(378):eaai8312CrossRefPubMed
73.
Pietzak EJ, Bagrodia A, Cha EK, Drill EN, Iyer G, Isharwal S et al (2017) Next-generation sequencing of nonmuscle invasive bladder cancer reveals potential biomarkers and rational therapeutic targets. Eur Urol
74.
Bitler BG, Aird KM, Garipov A, Li H, Amatangelo M, Kossenkov AV et al (2015) Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers. Nat Med 21(3):231–238CrossRefPubMed
75.
Jin F, Thaiparambil J, Donepudi SR, Vantaku V, Piyarathna DWB, Maity S et al (2017) Tobacco-specific carcinogens induce hypermethylation, DNA adducts, and DNA damage in bladder cancer. Cancer Prev Res (Phila) 10(10):588–597CrossRefPubMedCentral
76.
Shen C, Sun Z, Chen D, Su X, Jiang J, Li G et al (2015) Developing urinary metabolomic signatures as early bladder cancer diagnostic markers. OMICS 19(1):1–11CrossRefPubMedPubMedCentral
77.
Rosevear HM, Lightfoot AJ, O’Donnell MA, Griffith TS (2009) 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 28(3–4):345–353CrossRefPubMed
78.
Ratliff TL, Ritchey JK, Yuan JJ, Andriole GL, Catalona WJ (1993) T-cell subsets required for intravesical BCG immunotherapy for bladder cancer. J Urol 150(3):1018–1023CrossRefPubMed
79.
Biot C, Rentsch CA, Gsponer JR, Birkhauser FD, Jusforgues-Saklani H, Lemaitre F et al (2012) Preexisting BCG-specific T cells improve intravesical immunotherapy for bladder cancer. Sci Transl Med 4(137):137ra72CrossRefPubMed
80.
Kavoussi LR, Brown EJ, Ritchey JK, Ratliff TL (1990) Fibronectin-mediated Calmette–Guerin bacillus attachment to murine bladder mucosa. Requirement for the expression of an antitumor response. J Clin Invest 85(1):62–67CrossRefPubMedPubMedCentral
81.
Kamat AM, Li R, O’Donnell MA, Black PC, Roupret M, Catto JW et al (2018) Predicting response to intravesical bacillus Calmette–Guerin immunotherapy: are we there yet? A Systematic Review. Eur Urol 73(5):738–748CrossRefPubMed
82.
Lerner SP, Dinney C, Kamat A, Bivalacqua TJ, Nielsen M, O’Donnell M et al (2015) Clarification of bladder cancer disease states following treatment of patients with intravesical BCG. Bladder Cancer. 1(1):29–30CrossRefPubMed
83.
Inman BA, Sebo TJ, Frigola X, Dong H, Bergstralh EJ, Frank I et al (2007) PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer 109(8):1499–1505CrossRefPubMed
84.
Dinney CP, Fisher MB, Navai N, O’Donnell MA, Cutler D, Abraham A et al (2013) Phase I trial of intravesical recombinant adenovirus mediated interferon-alpha2b formulated in Syn3 for Bacillus Calmette–Guerin failures in nonmuscle invasive bladder cancer. J Urol 190(3):850–856CrossRefPubMedPubMedCentral
85.
Shore ND, Boorjian SA, Canter DJ, Ogan K, Karsh LI, Downs TM et al (2017) Intravesical rAd-IFNalpha/Syn3 for patients with high-grade, bacillus Calmette–Guerin-refractory or relapsed non-muscle-invasive bladder cancer: a phase II randomized study. J Clin Oncol 35(30):3410–3416CrossRefPubMedPubMedCentral
86.
Powles T, Necchi A, Rosen G, Hariharan S, Apolo AB (2018) Anti-programmed cell death 1/ligand 1 (PD-1/PD-L1) antibodies for the treatment of urothelial carcinoma: state of the art and future development. Clin Genitourin Cancer. 16(2):117–129CrossRefPubMed
87.
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK et al (2017) Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357(6349):409–413CrossRefPubMedPubMedCentral
88.
Teo MY, Seier K, Ostrovnaya I, Regazzi AM, Kania BE, Moran MM et al (2018) Alterations in DNA damage response and repair genes as potential marker of clinical benefit from PD-1/PD-L1 blockade in advanced urothelial cancers. J Clin Oncol 36(17):1685–1694CrossRefPubMedPubMedCentral
89.
Kardos J, Chai S, Mose LE, Selitsky SR, Krishnan B, Saito R et al (2016) Claudin-low bladder tumors are immune infiltrated and actively immune suppressed. JCI Insight. 1(3):e85902CrossRefPubMedPubMedCentral
90.
Kawahara T, Furuya K, Nakamura M, Sakamaki K, Osaka K, Ito H et al (2016) Neutrophil-to-lymphocyte ratio is a prognostic marker in bladder cancer patients after radical cystectomy. BMC Cancer. 16:185CrossRefPubMedPubMedCentral
91.
D’Andrea D, Moschini M, Gust K, Abufaraj M, Ozsoy M, Mathieu R et al (2017) Prognostic role of neutrophil-to-lymphocyte ratio in primary non-muscle-invasive bladder cancer. Clin Genitourin Cancer. 15(5):e755–e764CrossRefPubMed
92.
Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM et al (2015) Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350(6264):1084–1089CrossRefPubMedPubMedCentral
93.
Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV et al (2018) Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359(6371):97–103CrossRefPubMed
94.
Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R et al (2018) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359(6371):91–97CrossRefPubMed
95.
Zitvogel L, Ma Y, Raoult D, Kroemer G, Gajewski TF (2018) The microbiome in cancer immunotherapy: diagnostic tools and therapeutic strategies. Science 359(6382):1366–1370CrossRefPubMed
96.
Lamont FR, Tomlinson DC, Cooper PA, Shnyder SD, Chester JD, Knowles MA (2011) Small molecule FGF receptor inhibitors block FGFR-dependent urothelial carcinoma growth in vitro and in vivo. Br J Cancer 104(1):75–82CrossRefPubMed
97.
Hahn NM, Bivalacqua TJ, Ross AE, Netto GJ, Baras A, Park JC et al (2017) A phase II trial of dovitinib in BCG-unresponsive urothelial carcinoma with FGFR3 mutations or overexpression: hoosier cancer research network trial HCRN 12-157. Clin Cancer Res 23(12):3003–3011CrossRefPubMed
98.
Pal SK, Rosenberg JE, Hoffman-Censits JH, Berger R, Quinn DI, Galsky MD et al (2018) Efficacy of BGJ398, a fibroblast growth factor receptor 1-3 inhibitor, in patients with previously treated advanced urothelial carcinoma with FGFR3 alterations. Cancer Discov 8(7):812–821CrossRefPubMedPubMedCentral
99.
Rebouissou S, Bernard-Pierrot I, de Reynies A, Lepage ML, Krucker C, Chapeaublanc E 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(244):244ra91CrossRefPubMed
100.
Choudhury NJ, Campanile A, Antic T, Yap KL, Fitzpatrick CA, Wade JL 3rd et al (2016) Afatinib activity in platinum-refractory metastatic urothelial carcinoma in patients with ERBB alterations. J Clin Oncol 34(18):2165–2171CrossRefPubMedPubMedCentral
101.
Earl J, Rico D, Carrillo-de-Santa-Pau E, Rodriguez-Santiago B, Mendez-Pertuz M, Auer H et al (2015) The UBC-40 urothelial bladder cancer cell line index: a genomic resource for functional studies. BMC Genomics. 16:403CrossRefPubMedPubMedCentral
102.
Saito R, Smith CC, Utsumi T, Bixby LM, Kardos J, Wobker SE et al (2018) Molecular subtype-specific immunocompetent models of high-grade urothelial carcinoma reveal differential neoantigen expression and response to immunotherapy. Cancer Res 78(14):3954–3968CrossRefPubMedPubMedCentral
103.
Fantini D, Glaser AP, Rimar KJ, Wang Y, Schipma M, Varghese N et al (2018) A Carcinogen-induced mouse model recapitulates the molecular alterations of human muscle invasive bladder cancer. Oncogene 37(14):1911–1925CrossRefPubMedPubMedCentral
104.
Zhang ZT, Pak J, Shapiro E, Sun TT, Wu XR (1999) Urothelium-specific expression of an oncogene in transgenic mice induced the formation of carcinoma in situ and invasive transitional cell carcinoma. Cancer Res 59(14):3512–3517PubMed
105.
Puzio-Kuter AM, Castillo-Martin M, Kinkade CW, Wang X, Shen TH, Matos T et al (2009) Inactivation of p53 and Pten promotes invasive bladder cancer. Genes Dev 23(6):675–680CrossRefPubMedPubMedCentral
106.
Zhang ZT, Pak J, Huang HY, Shapiro E, Sun TT, Pellicer A et al (2001) Role of Ha-ras activation in superficial papillary pathway of urothelial tumor formation. Oncogene 20(16):1973–1980CrossRefPubMed
107.
Pan CX, Zhang H, Tepper CG, Lin TY, Davis RR, Keck J et al (2015) Development and characterization of bladder cancer patient-derived xenografts for molecularly guided targeted therapy. PLoS ONE 10(8):e0134346CrossRefPubMedPubMedCentral
108.
Sachs N, Clevers H (2014) Organoid cultures for the analysis of cancer phenotypes. Curr Opin Genet Dev 24:68–73CrossRefPubMed
109.
Lee SH, Hu W, Matulay JT, Silva MV, Owczarek TB, Kim K et al (2018) Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 173(2):515-28 e17CrossRef
110.
Ahmed M, Sottnik JL, Dancik GM, Sahu D, Hansel DE, Theodorescu D et al (2016) An osteopontin/CD44 axis in RhoGDI2-mediated metastasis suppression. Cancer Cell 30(3):432–443CrossRefPubMedPubMedCentral
111.
Roth B, Jayaratna I, Sundi D, Cheng T, Melquist J, Choi W et al (2017) Employing an orthotopic model to study the role of epithelial-mesenchymal transition in bladder cancer metastasis. Oncotarget. 8(21):34205–34222CrossRefPubMed
112.
Cheung KJ, Gabrielson E, Werb Z, Ewald AJ (2013) Collective invasion in breast cancer requires a conserved basal epithelial program. Cell 155(7):1639–1651CrossRefPubMedPubMedCentral
113.
Wang M, Yao LC, Cheng M, Cai D, Martinek J, Pan CX et al (2018) Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy. FASEB J. 32(3):1537–1549CrossRefPubMed
Metadata
Title
SIU–ICUD consultation on bladder cancer: basic science
Authors
David J. McConkey
Seth P. Lerner
Publication date
01-01-2019
Publisher
Springer Berlin Heidelberg
Published in
World Journal of Urology / Issue 1/2019
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-018-2594-y

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