Wnt/β-Catenin Signaling and Immunotherapy Resistance: Lessons for the Treatment of Urothelial Carcinoma

被引:35
作者
Chehrazi-Raffle, Alexander [1 ]
Dorff, Tanya B. [1 ]
Pal, Sumanta K. [1 ]
Lyou, Yung [1 ]
机构
[1] City Hope Comprehens Canc Ctr, Dept Med Oncol & Expt Therapeut, Duarte, CA 91010 USA
关键词
Wnt; beta-catenin; urothelial cancer; immune checkpoint inhibitor; immunotherapy resistance; TUMOR-ASSOCIATED MACROPHAGES; PHASE-III TRIAL; BETA-CATENIN; BLADDER-CANCER; PROGNOSTIC VALUE; E-CADHERIN; EXPRESSION; GENE; GEMCITABINE; TARGET;
D O I
10.3390/cancers13040889
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Urothelial cell carcinoma (UCC) is a significant public health burden. It accounts for approximately 90 percent of all bladder cancers with an estimated 200,000 annual deaths globally. Platinum based cytotoxic chemotherapy combinations are the current standard of care in the frontline setting for metastatic UCC. Even with these treatments the median overall survival is estimated to be about 15 months. Recently, immune checkpoint inhibitors (ICIs) have demonstrated superior clinical benefits compared to second line chemotherapy in UCC treatment. However only a minority of patients (similar to 20%) respond to ICIs, which highlights the need to better understand the mechanisms behind resistance. In this review, we (i) examine the pathophysiology of Wnt/beta-catenin signaling, (ii) discuss pre-clinical evidence that supports the combination of Wnt/beta-catenin inhibitors and ICI, and (iii) propose future combination treatments that could be investigated through clinical trials.
引用
收藏
页码:1 / 13
页数:13
相关论文
共 76 条
[1]   The role of WNT signalling in urothelial cell carcinoma [J].
Ahmad, I. .
ANNALS OF THE ROYAL COLLEGE OF SURGEONS OF ENGLAND, 2015, 97 (07) :481-486
[2]   Ras mutation cooperates with β-catenin activation to drive bladder tumourigenesis [J].
Ahmad, I. ;
Patel, R. ;
Liu, Y. ;
Singh, L. B. ;
Taketo, M. M. ;
Wu, X-R ;
Leung, H. Y. ;
Sansom, O. J. .
CELL DEATH & DISEASE, 2011, 2 :e124-e124
[3]   β-Catenin activation synergizes with PTEN loss to cause bladder cancer formation [J].
Ahmad, I. ;
Morton, J. P. ;
Singh, L. B. ;
Radulescu, S. M. ;
Ridgway, R. A. ;
Patel, S. ;
Woodgett, J. ;
Winton, D. J. ;
Taketo, M. M. ;
Wu, X-R ;
Leung, H. Y. ;
Sansom, O. J. .
ONCOGENE, 2011, 30 (02) :178-189
[4]   Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99] [J].
Albers, P. ;
Park, S. -I. ;
Niegisch, G. ;
Fechner, G. ;
Steiner, U. ;
Lehmann, J. ;
Heimbach, D. ;
Heidenreich, A. ;
Fimmers, R. ;
Siener, R. .
ANNALS OF ONCOLOGY, 2011, 22 (02) :288-294
[5]   Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma [J].
Bellmunt, J. ;
de Wit, R. ;
Vaughn, D. J. ;
Fradet, Y. ;
Lee, J. -L. ;
Fong, L. ;
Vogelzang, N. J. ;
Climent, M. A. ;
Petrylak, D. P. ;
Choueiri, T. K. ;
Necchi, A. ;
Gerritsen, W. ;
Gurney, H. ;
Quinn, D. I. ;
Culine, S. ;
Sternberg, C. N. ;
Mai, Y. ;
Poehlein, C. H. ;
Perini, R. F. ;
Bajorin, D. F. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (11) :1015-1026
[6]   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].
Bellmunt, Joaquim ;
Theodore, Christine ;
Demkov, Tomasz ;
Komyakov, Boris ;
Sengelov, Lisa ;
Daugaard, Gedske ;
Caty, Armelle ;
Carles, Joan ;
Jagiello-Gruszfeld, Agnieszka ;
Karyakin, Oleg ;
Delgado, Francois-Michel ;
Hurteloup, Patrick ;
Morsli, Nassim ;
Salhi, Yacine ;
Culine, Stephane ;
von der Maase, Hans .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (27) :4454-4461
[7]   LOCALIZATION OF THE GENE FOR FAMILIAL ADENOMATOUS POLYPOSIS ON CHROMOSOME-5 [J].
BODMER, WF ;
BAILEY, CJ ;
BODMER, J ;
BUSSEY, HJR ;
ELLIS, A ;
GORMAN, P ;
LUCIBELLO, FC ;
MURDAY, VA ;
RIDER, SH ;
SCAMBLER, P ;
SHEER, D ;
SOLOMON, E ;
SPURR, NK .
NATURE, 1987, 328 (6131) :614-616
[8]   LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells [J].
Brand, Almut ;
Singer, Katrin ;
Koehl, Gudrun E. ;
Kolitzus, Marlene ;
Schoenhammer, Gabriele ;
Thiel, Annette ;
Matos, Carina ;
Bruss, Christina ;
Klobuch, Sebastian ;
Peter, Katrin ;
Kastenberger, Michael ;
Bogdan, Christian ;
Schleicher, Ulrike ;
Mackensen, Andreas ;
Ullrich, Evelyn ;
Fichtner-Feigl, Stefan ;
Kesselring, Rebecca ;
Mack, Matthias ;
Ritter, Uwe ;
Schmid, Maximilian ;
Blank, Christian ;
Dettmer, Katja ;
Oefner, Peter J. ;
Hoffmann, Petra ;
Walenta, Stefan ;
Geissler, Edward K. ;
Pouyssegur, Jacques ;
Villunger, Andreas ;
Steven, Andre ;
Seliger, Barbara ;
Schreml, Stephan ;
Haferkamp, Sebastian ;
Kohl, Elisabeth ;
Karrer, Sigrid ;
Berneburg, Mark ;
Herr, Wolfgang ;
Mueller-Klieser, Wolfgang ;
Renner, Kathrin ;
Kreutz, Marina .
Cell Metabolism, 2016, 24 (05) :657-671
[9]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[10]   TCF/LEFs and Wnt Signaling in the Nucleus [J].
Cadigan, Ken M. ;
Waterman, Marian L. .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2012, 4 (11)