scholarly journals Progress in the Research and Targeted Therapy of ErbB/HER Receptors in Urothelial Bladder Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Dong Chen ◽  
Yunlin Ye ◽  
Shengjie Guo ◽  
Kao Yao
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Genetic Testing ◽  
Targeted Therapy ◽  
Systemic Therapy ◽  
Theoretical Basis ◽  
Urothelial Cells ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder

Bladder cancer is a lethal malignancy and a majority of bladder cancer arise from urothelial cells. Infiltration and metastasis are barriers for the radical cystectomy to achieve favored outcome and are the main cause of death. Systemic therapy, including chemotherapy, targeted therapy, and immunotherapy, is fundamental for these patients. erbB/HER receptors are found to be overexpressed in a subgroup of urothelial carcinoma, targeting erbB/HER receptors in these patients was found to be an efficient way in the era of genetic testing. To evaluate the role of erbB/HER receptors in bladder cancer, we reviewed the literature and ongoing clinical trials as regards to this topic to unveil the context of erbB/HER receptors in bladder cancer, which probably help to solidate the theoretical basis and might instruct further research.

scholarly journals Pure high-grade papillary urothelial bladder cancer: a luminal-like subgroup with potential for targeted therapy

2020 ◽  
Vol 43 (5) ◽  
pp. 807-819 ◽  
Author(s):  
Tician Schnitzler ◽  
Nadina Ortiz-Brüchle ◽  
Ursula Schneider ◽  
Isabella Lurje ◽  
Karolina Guricova ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Molecular Subtype ◽  
Genomic Alteration ◽  
High Grade ◽  
Urothelial Bladder Cancer ◽  
Non Invasive ◽  
Urothelial Bladder

Abstract Purpose Non-invasive high-grade (HG) bladder cancer is a heterogeneous disease that is characterized insufficiently. First-line Bacillus Calmette-Guérin instillation fails in a substantial amount of cases and alternative bladder-preserving treatments are limited, underlining the need to promote a further molecular understanding of non-invasive HG lesions. Here, we characterized pure HG papillary urothelial bladder cancer (pure pTa HG), a potential subgroup of non-invasive HG bladder carcinomas, with regard to molecular subtype affiliation and potential for targeted therapy. Methods An immunohistochemistry panel comprising luminal (KRT20, ERBB2, ESR2, GATA3) and basal (KRT5/6, KRT14) markers as well as p53 and FGFR3 was used to analyze molecular subtype affiliations of 78 pure pTa HG/papillary pT1(a) HG samples. In 66 of these, ERBB2 fluorescence in situ hybridization was performed. Additionally, targeted sequencing (31 genes) of 19 pTa HG cases was conducted, focusing on known therapeutic targets or those described to predict response to targeted therapies noted in registered clinical trials or that are already approved. Results We found that pure pTa HG/papillary pT1(a) HG lesions were characterized by a luminal-like phenotype associated with frequent (58% of samples) moderate to high ERBB2 protein expression, rare FGFR3 alterations on genomic and protein levels, and a high frequency (89% of samples) of chromatin-modifying gene alterations. Of note, 95% of pTa HG/papillary pT1 HG cases harbored at least one potential druggable genomic alteration. Conclusions Our data should help guiding the selection of targeted therapies for investigation in future clinical trials and, additionally, may provide a basis for prospective mechanistic studies of pTa HG pathogenesis.

Treatment of metastatic bladder cancer

2017 ◽  
Author(s):  
Fabio Calabrò ◽  
Cora N. Sternberg
Keyword(s):  
Bladder Cancer ◽  
Urothelial Cancer ◽  
Clinical Investigation ◽  
Good Prognosis ◽  
New Drugs ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder ◽  
Molecular Patterns ◽  
The Impact

Although bladder cancer is considered a chemosensitive malignancy, the prognosis of patients with metastatic disease is poor, with a median survival of approximately 12–14 months in good prognosis patients and with cure in only a minority. The addition of new drugs to the standard cisplatin-based regimens has not improved these outcomes. In this chapter, we highlight the role of chemotherapy and the impact of the new targeted agents in the treatment of metastatic bladder carcinoma. A better understanding of the underlying biology and the molecular patterns of urothelial bladder cancer has led to clinical investigation of several therapeutic targets. To date, these agents have yet to demonstrate an improvement in overall survival. Urothelial cancer is extremely sensitive to checkpoint inhibition with both anti PD-1 and anti PDL1 antibodies. The future seems brighter with the advent of these new therapies.

Association of FokI polymorphism of vitamin D receptor with urothelial bladder cancer in Tunisians: role of tobacco smoking and plasma vitamin D concentration

Tumor Biology ◽  
2015 ◽  
Vol 37 (5) ◽  
pp. 6197-6203 ◽  
Author(s):  
Mohamed Kacem Ben Fradj ◽  
Amani Kallel ◽  
Mohamed Mourad Gargouri ◽  
Mohamed Ali Ben Chehida ◽  
Ahmed Sallemi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bladder Cancer ◽  
Vitamin D Receptor ◽  
Tobacco Smoking ◽  
Plasma Vitamin ◽  
Urothelial Bladder Cancer ◽  
Foki Polymorphism ◽  
Urothelial Bladder

Role of consolidative radiotherapy for metastatic urothelial bladder cancer patients without progression and with no more than five residual metastatic lesions following first line systemic therapy: A retrospective analysis.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 454-454
Author(s):  
Amélie Aboudaram ◽  
Leonor Chaltiel ◽  
Damien Pouessel ◽  
Pierre Graff-Cailleaud ◽  
Nicolas Benziane ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Systemic Therapy ◽  
Definitive Treatment ◽  
Urothelial Bladder Cancer ◽  
First Line ◽  
Standard Analysis ◽  
Primary Tumors ◽  
Urothelial Bladder ◽  
Consolidative Radiotherapy ◽  
Line Chemotherapy

454 Background: Consolidative local treatment of the primary tumor and metastases in the treatment of metastatic malignancies has shown promising results in several types of primary tumors. The aim of this study is to assess consolidative radiotherapy to the bladder and to residual metastases among metastatic urothelial bladder cancer with no progression following first line systemic therapy, hypothesizing an increase in overall survival and in progression free survival. Methods: Between January 2005 and December 2018, patients who received standard first-line chemotherapy for the treatment of metastatic urothelial bladder cancer (mUBC) were retrospectively identified through the database of four Comprehensive Cancer Centers in France. Among them, patients with no disease progression following chemotherapy and with no more than 5 residual metastases were analyzed: patients who received subsequent radiotherapy (of EQD2Gy > 50Gy) to the bladder and residual metastases were included in the consolidative group (RT group), and the other patients were included in the observation group (OBS group). PFS and OS were determined from the start of the first-line chemotherapy using the Kaplan-Meier method. To account for the delay from chemotherapy initiation to consolidative radiotherapy, a Cox model with time-dependant covariates, and a 6-month landmark analyses were performed to examine OS and PFS. Results: A total of 91 patients with at least stable disease following chemotherapy and with no more than 5 residual metastases were analyzed: 51 in the RT group and 40 in the OBS group. Metachronous metastatic disease (following definitive treatment of localized UBC) was more frequent in the OBS group (19% vs 5%, p = 0.02); the median number of metastases in the RT group vs in the OBS group was: 2 (1-9) vs 3 (1-5) (p = 0.04) at metastatic presentation, and 1 (0-5) vs 2 (0-5) (p = 0.18) after completion of chemotherapy (residual lesions), respectively. Two grade 3 toxicities (3.9%) and no grade 4 toxicity were reported in the RT group. With a median follow up of 85.9 months (95% IC [36.7; 101.6]), median OS and PFS were 21.7 months (95% IC [17.1; 29.7]) and 11.1 months (95% IC [9.9; 14.1]) for the whole cohort, respectively. In multivariable analysis: consolidative RT in comparison with observation was associated with improved OS in both the standard analysis (HR = 0.47, p = 0.015) and in the 6-month landmark analysis (HR = 0.48, p = 0.026); and with improved PFS only in the standard analysis (HR = 0.49, p = 0.007). Conclusions: Consolidative radiotherapy for mUBC patients who have not progressed after chemotherapy and with limited residual disease seems to confer both OS and PFS advantage. Prospective data in that field with addition of avelumab are needed.

Potential role of glycovariants of urinary MUC1 and CEA in sensitive detection of urothelial bladder cancer

2019 ◽  
Vol 493 ◽  
pp. S140
Author(s):  
P. Syed ◽  
H. Kekki ◽  
J. Terävä ◽  
K. Gidwani ◽  
U. Lamminmäki ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Potential Role ◽  
Sensitive Detection ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder

scholarly journals Cell adhesion and urothelial bladder cancer: the role of cadherin switching and related phenomena

2015 ◽  
Vol 370 (1661) ◽  
pp. 20140042 ◽  
Author(s):  
Richard T. Bryan
Keyword(s):  
Bladder Cancer ◽  
Cell Adhesion ◽  
Cancer Progression ◽  
Cell Phenotype ◽  
Urothelial Bladder Cancer ◽  
Invasion And Metastasis ◽  
Cancer Stem Cell Phenotype ◽  
Urothelial Bladder ◽  
Strong Candidate

Cadherins are mediators of cell–cell adhesion in epithelial tissues. E-cadherin is a known tumour suppressor and plays a central role in suppressing the invasive phenotype of cancer cells. However, the abnormal expression of N- and P-cadherin (‘cadherin switching’, CS) has been shown to promote a more invasive and m̀alignant phenotype of cancer, with P-cadherin possibly acting as a key mediator of invasion and metastasis in bladder cancer. Cadherins are also implicated in numerous signalling events related to embryonic development, tissue morphogenesis and homeostasis. It is these wide ranging effects and the serious implications of CS that make the cadherin cell adhesion molecules and their related pathways strong candidate targets for the inhibition of cancer progression, including bladder cancer. This review focuses on CS in the context of bladder cancer and in particular the switch to P-cadherin expression, and discusses other related molecules and phenomena, including EpCAM and the development of the cancer stem cell phenotype.

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