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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Notch signaling pathway in cancer: from mechanistic insights to targeted therapies

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Май 27, 2024

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The receptor ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical signaling transduction. Accumulating evidence indicates that the pathway serves as both an oncogenic factor a tumor suppressor various cancer types. Dysregulation of this promotes epithelial-mesenchymal transition angiogenesis malignancies, closely linked proliferation, invasion, metastasis. Furthermore, contributes maintaining stem-like properties cells, thereby enhancing invasiveness. regulatory metabolic reprogramming microenvironment suggests pivotal involvement balancing suppressive effects. Moreover, implicated conferring chemoresistance cells. Therefore, comprehensive understanding these biological processes crucial developing innovative therapeutic strategies targeting signaling. This review focuses on research progress cancers, providing in-depth insights into potential mechanisms regulation occurrence progression cancer. Additionally, summarizes pharmaceutical clinical trials therapy, aiming offer new human malignancies.

Язык: Английский

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Narrow Bandgap Schottky Heterojunction Sonosensitizer with High Electron–Hole Separation Boosted Sonodynamic Therapy in Bladder Cancer

Advanced Materials, Год журнала: 2024, Номер 36(26)

Опубликована: Март 29, 2024

Abstract Sonodynamic therapy (SDT) is applied to bladder cancer (BC) given its advantages of high depth tissue penetration and nontoxicity due the unique anatomical location near abdominal surface. However, low electron–hole separation efficiency wide bandgap sonosensitizers limit effectiveness SDT. This study aims develop a TiO 2 ‐Ru‐PEG Schottky heterojunction sonosensitizer with narrow for SDT in BC. Density functional theory (DFT) calculations experiments collectively demonstrate that reduced characteristic crystalline‐amorphous interface formed by deposition ruthenium (Ru) within shell layer . Thanks enhancement oxygen adsorption efficient pairs, promotes generation reactive species (ROS) under ultrasound (US) irradiation, resulting cell cycle arrest apoptosis tumor cells. The vivo results prove boosted subcutaneous orthotopic models while exhibiting good safety. adopts complex optimizing sonosensitizers, contributing progress improvement strategies presenting paradigm BC therapy.

Язык: Английский

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Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the “all-around warrior” in immunotherapy

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Сен. 2, 2024

Programmed death receptor-1 (PD-1) and its ligand, programmed ligand-1 (PD-L1) are essential molecules that key in modulating immune responses. PD-L1 is constitutively expressed on various cells, epithelial cancer where it functions as a co-stimulatory molecule capable of impairing T-cell mediated Upon binding to PD-1 activated T-cells, the PD-1/PD-L1 interaction triggers signaling pathways can induce apoptosis or anergy, thereby facilitating escape tumors. In urological cancers, including bladder (BCa), renal cell carcinoma (RCC), prostate (PCa), upregulation has been demonstrated. It linked poor prognosis enhanced tumor evasion. Recent studies have highlighted significant role axis mechanisms cancers. The between T-cells further contributes immunosuppression by inhibiting activation proliferation. Clinical applications checkpoint inhibitors shown promising efficacy treating advanced significantly improving patient outcomes. However, resistance these therapies, either intrinsic acquired, remains challenge. This review aims provide comprehensive overview pathway We summarize regulatory mechanism underlying expression activity, genetic, epigenetic, post-transcriptional, post-translational modifications. Additionally, we discuss current clinical research inhibitors, their therapeutic potential, challenges associated with resistance. Understanding crucial for developing new strategies overcome limitations enhance immunotherapy.

Язык: Английский

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The Role of SWI/SNF Complex in Bladder Cancer

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(1)

Опубликована: Янв. 1, 2025

ABSTRACT Bladder cancer originates from bladder tissues and is the ninth most common type of worldwide. The SWI/SNF (SWItch/sucrose non‐ fermentable) complex plays a crucial role in regulating various biological processes, such as cell cycle control, DNA damage repair transcription regulation. purpose this article to examine functional studies cancer, highlighting new pathways for creating personalised treatment approaches patients with mutations complex. By acquiring comprehensive understanding mechanisms we can offer more precise effective solutions treat disease.

Язык: Английский

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Urinary DNA Methylation Test for Bladder Cancer Diagnosis

JAMA Oncology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Importance An accurate noninvasive biomarker test is needed for the early diagnosis of bladder cancer. Objective To evaluate performance a urinary DNA methylation ( PENK methylation) and compare its diagnostic accuracy with that nuclear matrix protein 22 (NMP22) or urine cytology test. Design, Setting, Participants In this prospective multicenter study at 10 sites in Republic Korea, individuals 40 years older hematuria undergoing cystoscopy within 3 months between March 11, 2022, May 30, 2024, participated. The participants were evaluated cancer using Exposure Urinary test, NMP22 Main Outcomes Measures primary outcomes sensitivity specificity high-grade invasive Secondary objectives included overall (all stages grades) comparison sensitivities specificities Results Among 1099 participants, 614 (55.9%) male; had mean (SD) age 65 (10) years. Of 219 176 cancer, respectively. 89.2% (95% CI, 84.6%-93.8%) 87.8% 85.6%-89.9%), Sensitivity 78.1% 72.6%-83.6%) 88.8% 86.7%-90.8%), positive predictive value was 61.3% 55.4%-67.3%), negative 97.6% 96.6%-98.7%). showed significantly superior Conclusions Relevance hematuria, 89% detecting outperforming high specificity. While an excellent value, suboptimal.

Язык: Английский

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Impact of tumour stroma-immune interactions on survival prognosis and response to neoadjuvant chemotherapy in bladder cancer

EBioMedicine, Год журнала: 2024, Номер 104, С. 105152 - 105152

Опубликована: Май 9, 2024

The tumour stroma is associated with unfavourable prognosis in diverse solid tumours, but its prognostic and predictive value bladder cancer (BCa) unclear.

Язык: Английский

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Comprehensive genomic characterization of early-stage bladder cancer

Nature Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Язык: Английский

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The combination treatment of RC48 and STAT3 inhibitor acts as a promising therapeutic strategy for basal bladder cancer

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 7, 2025

As an antibody-drug conjugate (ADC), disitamab vedotin (RC48) is a promising treatment targeting ERBB2 for locally advanced and metastatic bladder cancer (BLCA). However, the subtype heterogeneity of muscle-invasive (MIBC) often leads to different therapeutic outcomes. In our study, we aim explore sensitivity differences mechanisms molecular subtypes MIBC RC48 develop strategy combination therapy against cancer. Using large-scale mRNA expression profile datasets, Western blotting, immunohistochemistry, first found that upregulated in luminal type but downregulated basal addition, cells showed higher than cells. Basal with overexpression demonstrated increased vitro vivo, indicating mediates RC48's efficacy or RC48-exposed cells, JAK/STAT3 pathway was highly enriched, suggesting downregulation pharmacological inhibition compensatory activation this pathway. Silencing STAT3 inhibitory RC48. artesunate (ART, inhibitor) synergistic effect both vivo. summary, these findings provide theoretical foundation subsequent clinical trials combining ART based on subtypes.

Язык: Английский

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Study of urine-based mRNA biomarkers for early detection of nonmuscle invasive bladder cancer (NMIBC)

Urologic Oncology Seminars and Original Investigations, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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