New Perspectives on the Role of Liquid Biopsy in Bladder Cancer: Applicability to Precision Medicine

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 803 - 803

Published: Feb. 16, 2024

Bladder cancer (BC) is one of the most common tumors in world. Cystoscopy and tissue biopsy are standard methods screening early diagnosis suspicious bladder lesions. However, they invasive procedures that may cause pain infectious complications. Considering limitations both procedures, recurrence resistance to BC treatment, it necessary develop a new non-invasive methodology for multiple evaluations patients under follow-up cancer. In recent years, liquid has proven be very useful diagnostic tool detection tumor biomarkers. This technique makes possible analyze single components released into peripheral circulation monitor progression. Numerous biomarkers being studied interesting clinical applications these presented, with promising results diagnosis, microscopic disease, prediction response treatment.

Language: Английский

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A novel CD8+ T cell-related gene signature for predicting the prognosis and immunotherapy efficacy in bladder cancer

Inflammation Research, Journal Year: 2023, Volume and Issue: 72(8), P. 1665 - 1687

Published: Aug. 1, 2023

Language: Английский

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Current Landscape of Immune Checkpoint Inhibitors for Metastatic Urothelial Carcinoma: Is There a Role for Additional T-Cell Blockade?

Cancers, Journal Year: 2023, Volume and Issue: 16(1), P. 131 - 131

Published: Dec. 27, 2023

Urothelial carcinoma (UC) is the most common form of bladder cancer (BC) and variant with immunogenic response. This makes urothelial an ideal candidate for immunotherapy immune checkpoint inhibitors. Key proteins PD-1 CTLA-4 are frequently expressed on T-cells in carcinoma. The blockade this can lead to reactivation lymphocytes augment anti-tumor only inhibitors that FDA-approved metastatic target programmed death-1 receptor its ligand (PD-1/PD-L1) axis. However, overall response rate progression-free survival rates these agents limited patient population. Therefore, there a need find further immune-bolstering treatment combinations may positively impact patients advanced UC. In review, current inhibition landscape explored emphasis combination therapy PD-1/PD-L1 blockade. investigation literature found preclinical data show decrease tumor volumes size when blocked, similar results were observed investigations evaluating We anticipate review provide foundation deeper experimental into

Language: Английский

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Molecular classification of muscle-invasive bladder cancer based on a simplified immunohistochemical panel using GATA3, CK5/6 and p16

Biomolecules and Biomedicine, Journal Year: 2023, Volume and Issue: unknown

Published: June 21, 2023

The choice of therapy for muscle-invasive bladder cancer (MIBC) could be influenced by the tumor’s molecular subtype. Currently, well-defined consensus subtypes are based on tumor microarray mRNA data. Clearly defined and easy-to-use surrogate subtypes, immunohistochemistry (IHC) performed whole slides, needed to make subtyping cost-effective useful in routine work future research. To aid development a simple immunohistochemical classifier, retrospective single-center series 92 cases localized was identified. Routine IHC GATA3, cytokeratins 5 6 (CK5/6), p16 tissue blocks containing disease. Electronic medical records were retrieved searched clinical variables, treatment, survival mean age 69.6 years, 73% males. Conservative treatment used 55% cases, while cystectomy with chemotherapy 45%. GATA3 CK5/6 expression divided into broad luminal basal respectively, subclassify papillary unstable types according classification. When subtyped this way, negative showed worse overall survival. Molecular MIBC slides using only three commonly used, consensus-based antibodies, is feasible method detecting invasive cancer. Future combining morphological analysis fully translate classification comprehensive, strategy.

Language: Английский

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Integrating the PD-L1 Prognostic Biomarker in Non-Muscle Invasive Bladder Cancer in Clinical Practice—A Comprehensive Review on State-of-the-Art Advances and Critical Issues

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(8), P. 2182 - 2182

Published: April 10, 2024

Bladder cancer (BC) is one of the most prevalent cancers worldwide. Non-muscle invasive bladder (NMIBC), comprising majority initial BC presentations, requires accurate risk stratification for optimal management. This review explores evolving role programmed cell death ligand 1 (PD-L1) as a prognostic biomarker in NMIBC, with particular focus on its implications context Bacillus Calmette-Guérin (BCG) immunotherapy. The literature suggests potential association between elevated PD-L1 status and adverse outcomes, resistance to BCG treatment, disease progression. However, conflicting findings methodological issues highlight heterogeneity assessment probably due complex biological mechanisms that regulate interaction tumor microenvironment. identification provides ground tailored therapeutic interventions, including immune checkpoint inhibitors (ICIs). Nevertheless, challenges such intratumoral technical underscore need standardized protocols larger, homogeneous trials. contributes ongoing debate personalized management NMIBC patients, focusing advances perspectives incorporating this setting.

Language: Английский

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The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder Cancer

Diagnostics, Journal Year: 2024, Volume and Issue: 14(22), P. 2501 - 2501

Published: Nov. 8, 2024

Bladder cancer (BC) is a highly heterogeneous disease, presenting clinical challenges, particularly in predicting patient outcomes and selecting effective treatments. Molecular subtyping has emerged as an essential tool for understanding the biological diversity of BC; however, its implementation practice remains limited due to high costs complexity genomic techniques. This review examines role immunohistochemistry (IHC) surrogate marker molecular BC, highlighting potential bridge gap between advanced classifications routine application; Methods: We explore evolution taxonomic classification with particular focus on cytokeratin (KRT) expression patterns normal urothelium, which are key identifying basal luminal subtypes. Furthermore, we emphasise need consensus IHC markers reliably define these subtypes, facilitating wider standardised use. The also analyses application both muscle-invasive (MIBC) non-muscle-invasive bladder (NMIBC), attention less extensively studied NMIBC cases. discuss practical advantages subtyping, including cost effectiveness feasibility standard pathology laboratories, alongside ongoing challenges such requirement protocols external validation across diverse settings; Conclusions: While limitations, it offers viable alternative laboratories lacking access Further research required determine optimal combination markers, establish diagnostic algorithm, validate through large-scale trials. will ultimately enhance accuracy, guide treatment decisions, improve outcomes.

Language: Английский

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The role of immunohistochemical analysis in determining the molecular subtypes of bladder cancer

Advances in molecular oncology, Journal Year: 2024, Volume and Issue: 11(4), P. 102 - 113

Published: Dec. 10, 2024

Introduction. The results of genomic profiling muscle-invasive bladder cancer (BC) based on messenger RNA (mRNA) extraction showed significant molecular variety the tumors underlying wide spectrum clinical manifestations and responses to traditional treatment methods. However, despite valuableness mRNA for understanding biological behavior tumor, its implementation in routine practice is complicated due technological complexity high cost sequencing. Therefore, determination BC subtype immunohistochemical examination can be considered an alternative profiling. method should validated using material. Aim. To evaluate prognostic significance urothelial a surrogate panel consisting 13 markers semiquantitative calculation histochemical index. Materials retrospective cohort study included 49 patients with who underwent radical cystectomy (RC) after previous transurethral resection (TURBT) between 2013 2016 at center. inclusion criteria were patient age 18 75 years, histologically verified BC, availability formalin-fixed paraffin embedded blocks TURBT RC Clinical Laboratory Morphology. exclusion rare histological types grade IV–V surgical complications per Clavien–Dindo classification during hospitalization, performed other medical facilities. Molecular subtypes determined Ventana BenchMark XT (Roche, USA) immunostainer technique deparaffinized sections subtype-specific antibodies recommended by Lund taxonomy (LundTax). Depending hyperexpression level basal and/or luminal antibodies, 4 identified: А (UroA), В (UroB), genomically unstable (GU). first endpoint was 5-year recurrence-free survival material, secondary overall same Results. Using analysis marker preserved material TURBT, 38 (77.6 %) patients, – 39 (79.5 patients. Percentages UroA, UroB GU almost identical; rarest type Basal (8.2 5 (10.2 cases, respectively. Evaluation primary that ( log-rank test; p = 0.85) 0.95) did not differ various subtypes. show statistical difference OS 1 0.94) 2 0.92). Multivariate regression most predictors recurrence stage IIIA 0.017) pathomorphological II 0.021), while rates significantly affected stages 0.003) IVA 0.019). Conclusion. Determination index effectiveness significance: identified affect long-term oncological outcomes.

Language: Английский

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Similar genetic profile in early and late stage urothelial tract cancer

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(7)

Published: July 8, 2024

Abstract Introduction Urothelial tract cancer (UTC) ranks as the tenth most prevalent and holds seventh position in terms of mortality worldwide. Despite its prevalence ranking, there are still gaps knowledge mutational landscape patients with advanced disease who have limited therapeutic options after multiple lines prior treatment. This study compares genomic transcriptomic landscape, targeted treatment between metastatic UTC (mUTC) treated therapy compared to newly diagnosed, untreated Muscle Invasive Bladder Cancer (MIBC). Methods We clinical data from two cohorts: mUTC received were referred Copenhagen Prospective Personalized Oncology (CoPPO) project at Rigshospitalet, University Copenhagen. Data for MIBC acquired Genome Atlas (TCGA BLCA) cohort. Biopsies CoPPO performed time enrollment. 523 highly important cancer-related genes (TrueSight Oncology-500 sequencing panel) used both cohorts comparative analysis. Analyses included RNA count compare predicted molecular subtypes each cohort separately. Results Patients had a lower median age first-line than TCGA BLCA cohort, no significant gender disparity. The predominant histology was urothelial cell carcinoma cohorts. Genomic analysis revealed difference top mutated cohorts, specifically looking into DNA damage repair genes. Molecular subtyping indicated higher frequency neuroendocrine differentiation 13% based on findings, 16% non-targeted treatment, totaling 29% receiving (9 patients). remaining 71% best supportive care. Kaplan-Meier showed non-significant survival benefit intervention group Conclusion When focusing relevant genes, profile undergone numerous resembles that diagnosed MIBC. These alterations can be targeted, indicating potential advantage early testing personalized within trials.

Language: Английский

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