Advances in diagnosis and treatment of bladder cancer

BMJ, Год журнала: 2024, Номер unknown, С. e076743 - e076743

Опубликована: Фев. 12, 2024

Abstract Bladder cancer remains a leading cause of death worldwide and is associated with substantial impacts on patient quality life, morbidity, mortality, cost to the healthcare system. Gross hematuria frequently precedes diagnosis bladder cancer. Non-muscle-invasive (NMIBC) managed initially transurethral resection tumor (TURBT), followed by risk stratified approach adjuvant intravesical therapy (IVe), an overall survival 90%. However, cure rates remain lower for muscle invasive (MIBC) owing variety factors. NMIBC MIBC groupings are heterogeneous have unique pathological molecular characteristics. Indeed, The Cancer Genome Atlas project identified genetic drivers luminal basal subtypes distinct treatment responses. For NMIBC, IVe immunotherapy (primarily BCG) gold standard high grade reduce or prevent both recurrence progression after initial TURBT; novel trials incorporate immune checkpoint inhibitors. gene combination chemotherapy recently been completed, promising results. localized MIBC, essential goals improving care reducing morbidity following cystectomy preserving strategies. In metastatic disease, advances in understanding genomic landscape microenvironment led implementation inhibitors, targeted treatments, antibody-drug conjugates. Defining better selection criteria identify patients most likely benefit from specific urgent need.

Язык: Английский

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Prognostic and predictive role of circulating tumor DNA detection in patients with muscle invasive bladder cancer: a systematic review and meta-analysis

Cancer Cell International, Год журнала: 2025, Номер 25(1)

Опубликована: Март 1, 2025

At present, there is no effective prognostic indicator for muscle invasive bladder cancer (MIBC). A liquid biopsy method, plasma circulating tumor DNA (ctDNA) detection, was evaluated use in predicting the prognosis of different cancers. This study aims to assess value ctDNA state muscle-invasive patients. We comprehensively searched three public databases (PubMed, EMBASE, and Cochrane Library) December 2023 according Preferred Reporting Items Systematic Review Meta-analysis (PRISMA) statement. Studies investigating outcome indicators patients with MIBC were included our analysis. The hazard ratios (HRs) 95% confidence intervals (CIs) extracted evaluate association between MIBC. Eleven studies 1,170 diagnosed cancer, comprising a total four retrospective cohort eight prospective studies, meta-analysis, one which had two cohorts. analysis revealed that positive associated poor overall survival (OS), progression-free (PFS), recurrence-free (RFS) (HR = 4.51, CI: 2.64–7.69, P < 0.001; HR 4.50, 2.77–7.30, 6.56, 4.18–10.30, 0.001), significant effects both pre- post-treatment. In addition, longitudinal proved be monitoring receiving treatments 0.24, 0.14–0.41, 0.001). OS, PFS, RFS Meanwhile, clearance improved These findings suggest predictive MIBC, can used monitor recurrence guide treatment. Thus, level detection shows potential treatment

Язык: Английский

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Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current Development

Biomedicines, Год журнала: 2025, Номер 13(1), С. 86 - 86

Опубликована: Янв. 1, 2025

Urothelial carcinoma (UC) is the most common histological subtype of bladder tumors; however, cancer represents a heterogeneous group diseases with at least 40 distinct subtypes. Among these, 2022 World Health Organization classification urinary tract tumors identifies range less subtypes invasive UC, formerly known as variants, which are considered high-grade tumors, including squamous cell, small-cell, sarcomatoid urothelial, micropapillary, plasmacytoid, and urachal carcinomas, adenocarcinoma. Their accurate diagnosis critical for risk stratification therapeutic decision-making, histologies associated poorer outcomes than conventional UC. Despite importance precise diagnosis, high-quality evidence on optimal treatments remains limited owing to their rarity. In particular, neoadjuvant adjuvant chemotherapy have not been well characterized, prospective data scarce. For advanced-stage diseases, clinical trial participation strongly recommended address lack robust evidence. Advances in molecular pathology development targeted therapies immunotherapies reshaped our understanding subtypes, spurring efforts identify predictive biomarkers guide personalized treatment strategies. Nevertheless, management rare subgroups challenging because they frequently excluded from trials. localized disease, curative options such surgical resection or radiotherapy available; become more recurrence metastasis, where systemic therapy primarily used control disease progression palliate symptoms. Herein, we present recent advances urothelial non-urothelial also explore current guiding emphasize challenges perspectives future

Язык: Английский

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Repurposing ProTAME for Bladder Cancer: A Combined Therapeutic Approach Targeting Cell Migration and MMP Regulation

Biology, Год журнала: 2025, Номер 14(3), С. 263 - 263

Опубликована: Март 5, 2025

Bladder cancer, the fourth most common cancer type among men, remains a therapeutic challenge due to its heterogeneity and frequent development of chemoresistance. Cisplatin-based chemotherapy, often combined with gemcitabine, is standard treatment, yet resistance off-target effects in non-cancerous tissues limit efficacy. This study evaluated cisplatin, APC/C inhibitor proTAME, both individually combination, on cell migration MMP2/MMP9 expression RT4 bladder ARPE-19 normal epithelial cells. Molecular docking analyses were conducted investigate interactions these compounds MMP2 MMP9. IC20 values for proTAME applied scratch-wound healing quantitative real-time PCR (qRT-PCR) assays. Docking results predicted that may interact favorably (−9.2 kcal/mol) MMP9 (−8.7 kcal/mol), showing high computational binding affinities potential key hydrogen bonds; however, require further experimental validation. Scratch-wound qRT-PCR assays demonstrated proTAME-containing combinations associated reduced decreased Cisplatin showed pronounced reduction MMP migration, alone also exhibiting notable inhibitory effects. In cells, gemcitabine cisplatin upregulated expression, suggesting stress response, whereas mitigated this effect. These differential show importance tumor-specific responses where shows promise enhancing efficacy chemotherapy by modulating MMP-related pathways involved tumor invasion. conclusion, highlights as repurposed agent treatment association downregulation. While vitro silico findings suggest promising role combination therapies, validation advanced preclinical models necessary assess applicability safety.

Язык: Английский

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TP53 disruptive mutation predicts platinum‐based chemotherapy and PD‐1/PD‐L1 blockade response in urothelial carcinoma

The Journal of Pathology, Год журнала: 2024, Номер 263(2), С. 139 - 149

Опубликована: Фев. 21, 2024

TP53 mutation is one of the most common genetic alterations in urothelial carcinoma (UrCa), and heterogeneity mutants leads to heterogeneous clinical outcomes. This study aimed investigate relevance specific mutations UrCa. In this study, a total eight cohorts were enrolled, along with matched annotation. classified as disruptive nondisruptive according degree disturbance p53 protein function structure. We evaluated significance our local datasets publicly available datasets. The co-occurring events UrCa, their therapeutic indications, functional effects, tumor immune microenvironment, also investigated. identified 49.7% UrCa patients. Within group, 25.1% patients carried

Язык: Английский

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Investigation toward the economic feasibility of personalized medicine for healthcare service providers: the case of bladder cancer

Frontiers in Medicine, Год журнала: 2024, Номер 11

Опубликована: Май 14, 2024

In today's complex healthcare landscape, the pursuit of delivering optimal patient care while navigating intricate economic dynamics poses a significant challenge for service providers (HSPs). this already dynamic, emergence clinically promising personalized medicine-based treatment aims to revolutionize medicine. While medicine holds tremendous potential enhancing therapeutic outcomes, its integration within resource-constrained HSPs presents formidable challenges. study, we investigate feasibility implementing The central objective is strike balance between catering individual needs and making economically viable decisions. Unlike conventional binary approaches treatment, propose more nuanced perspective by treating personalization as spectrum. This approach allows greater flexibility in decision-making resource allocation. To end, mathematical framework our proposal, focusing on Bladder Cancer (BC) case study. Our results show that it feasible introduce medicine, highly efficient but expensive one would be short-lived relative less effective cheaper alternative latter can provided larger cohort patients, optimizing HSP's better.

Язык: Английский

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Niacin Ester Derivative of Brefeldin A as a Potential Dual-Target Arf1/BMX Inhibitor for Bladder Cancer

Journal of Natural Products, Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

Bladder cancer is a common malignancy known for its high recurrence rate and poor survival rate. New strategies are urgently needed to reduce improve prognosis. Arf1 BMX potential targets associated with the prognosis of bladder cancer. In this study, niacin ester derivatives brefeldin A were synthesized by introducing nicotinic acid moieties at 4-OH 7-OH positions. Notably, 4-monoester derivative, CHNQD-01228 (2), could significantly inhibit proliferation T24 cells (IC50 = 0.22 μM) in time-dependent manner. Furthermore, it dose-dependently inhibited cell migration colony formation, induced G1 phase arrest, triggered apoptosis. Based on molecular modeling, was evaluated exhibit binding affinity toward both proteins. Further verification conducted using cellular thermal shift assays drug responsive target stability assays. It suppressed AKT/p-AKT STAT3/p-STAT3 signaling pathways targeting cells, eliminated stem activated antitumor immunity via inhibition. vivo data further demonstrated that dual-target inhibitor exhibited efficacy against MB49 allograft tumors (TGI 51.0%) thus represents promising therapeutic strategy

Язык: Английский

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Current and Emerging Strategies to Treat Urothelial Carcinoma

Cancers, Год журнала: 2023, Номер 15(19), С. 4886 - 4886

Опубликована: Окт. 8, 2023

Urothelial cell carcinoma (UCC, bladder cancer, BC) remains a difficult-to-treat malignancy with rising incidence worldwide. In the U.S., UCC is sixth most incident neoplasm and ~90% of diagnoses are made in those >55 years age; it ~four times more commonly observed men than women. The important risk factor for developing BC tobacco smoking, which accounts ~50% cases, followed by occupational exposure to aromatic amines ionizing radiation. standard care advanced includes platinum-based chemotherapy programmed death (PD-1) or ligand 1 (PD-L1) inhibitors, administered as frontline, second-line, maintenance therapy. generally incurable associated intrinsic acquired drug immune resistance. lethal metastatic state characterized genomic instability, high PD-L1 expression, DNA damage-response mutations, tumor mutational burden. Although checkpoint inhibitors (ICIs) achieve long-term durable responses other cancers, their ability similar results (mUCC) not well-defined. Here, we discuss therapies improve management how comprehensive profiling can identify actionable biomarkers eventually fulfill promise precision medicine patients.

Язык: Английский

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Advancing Leukemia Management Through Liquid Biopsy: Insights into Biomarkers and Clinical Utility

Cancers, Год журнала: 2025, Номер 17(9), С. 1438 - 1438

Опубликована: Апрель 25, 2025

Liquid biopsy is classically defined as the detection of biomarkers in bodily fluids. One these can be circulating cell-free DNA (cfDNA) released by healthy or cancer cells during apoptosis. These fragments quantified and molecularly characterized techniques like digital droplet PCR (ddPCR) next-generation sequencing (NGS). By identifying common genetic epigenetic alterations associated with specific types, cfDNA tumor (ctDNA) serve robust for monitoring initiation progression. Other biomarkers, such microRNAs (miRNAs), extracellular vesicles, (CTCs) are also applied this context. has gained attention a versatile tool diagnostics, prognosis, therapeutic monitoring, minimal residual disease (MRD) across various malignancies, including hematological cancers myeloid lymphoid leukemias. Herein, we present comprehensive review liquid usage leukemia, focus on clinical utility ctDNA, miRNAs, exosomes treatment response, tracking clonal evolution, detecting disease. Our emphasizes translational implications tools improving patient outcomes outlines current challenges their integration into practice.

Язык: Английский

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Advances, recognition, and interpretation of molecular heterogeneity among conventional and subtype histology of urothelial carcinoma (UC): a survey among urologic pathologists and comprehensive review of the literature

Histopathology, Год журнала: 2024, Номер 85(5), С. 748 - 759

Опубликована: Июль 29, 2024

Aims Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding signatures to the morphologic diagnosis. As morphology associated repertoire may potentially translate choices of response therapy relapse rate, broader acceptability recognizing these key features among uropathologists is needed. This prompted an international survey ascertain practice patterns in classical/subtype UC across globe. Methods Results A instrument was shared 98 using SurveyMonkey software. Anonymized respondent data were analysed. rate 85%. majority concordance with profiles luminal (93%) basal (82%) types. Opinion on FGFR3 testing platform variable. While 95% concurred that TERT promoter mutation driver UC, 72% had opinion APOBEC mutagenesis main signature muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions MIBC ERCC2 mutations. Among participants, 94% would quantify aggressive micropapillary sarcomatoid histology, while 88% reevaluate another transurethral resection tumour specimen nonmuscle micropapillary, small cell, or histology. leading number agreed specific (93%), plasmacytoid (97%), cell (86%) subtypes. Ninety‐six percent participants a small‐cell component portends more course should be treated neoadjuvant chemotherapy 63% perform HER2/neu only oncologist's request advanced tumours. Ninety microsatellite instability testing, although not standard protocol, considered young patients upper tract UC. Eighty‐six high mutational burden better candidate for immunotherapy. Conclusion In era precision medicine, enhanced understanding heterogeneity will contribute therapeutic options, novel biomarker discovery, innovative management protocols, outcomes. Our provides broad perspective pathologists' perceptions experience regarding incorporation histomolecular approaches “personalize” therapy. Due variable clinical adoption, there need additional uniform study criteria. drive generation best guidelines this area widespread consistent utility.

Язык: Английский

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