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Background: Bladder cancer poses a significant global health challenge, with a complex pathogenesis that includes a subpopulation of cancer stem cells (CSCs) contributing to therapy resistance and tumor recurrence. Identifying and understanding the role of CSC markers are crucial for developing targeted therapies and improving prognosis.
Objective: This systematic review and meta-analysis aimed to assess the clinicopathological significance and prognostic value of CSC markers in patients with bladder cancer.
Methods: A comprehensive literature search was performed according to PRISMA guidelines, identifying studies that evaluated CSC markers in bladder cancer. The methodological quality of included studies was assessed using the Newcastle-Ottawa Scale, and data were extracted for quantitative analysis.
Results: In total, 13 studies were included in the final analysis, covering a range of CSC markers including CD44, CD44v9, Nanog, Sox2, ALDH1, ALDH1A1, Sox4, Notch-1, and Oct-4. The expression of CD44, CD44v9, and ALDH1A1 was significantly associated with poor survival outcomes. The combined expression of CD44 and Nanog emerged as an independent prognostic factor for recurrence-free survival. Additionally, Sox2, Sox4, Notch-1, and Oct-4 were found to be correlated with tumor progression and aggressiveness.
Conclusions: Certain CSC markers, notably CD44, CD44v9, and ALDH1A1, are significantly associated with adverse survival outcomes in bladder cancer. These markers could serve as potential prognostic indicators and therapeutic targets. Further research is needed to elucidate the roles of Sox2, Sox4, Notch-1, and Oct-4 in bladder cancer prognosis.
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http://dx.doi.org/10.1245/s10434-025-17600-6 | DOI Listing |
Nat Rev Urol
September 2025
Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Low-grade non-muscle invasive bladder cancer is a specific category of bladder cancer with a favourable prognosis; however, its management presents several challenges. The risk of stage progression is very low, but approximately half of patients will experience recurrence within the first 5 years after diagnosis. This high propensity for recurrence, coupled with the threat of progression, mandates ongoing surveillance.
View Article and Find Full Text PDFNat Commun
September 2025
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
With the approval of the antibody-drug conjugate enfortumab vedotin (EV), NECTIN4 has emerged as a bona fide therapeutic target in urothelial carcinoma (UC). Here, we report the development of a NECTIN4-directed chimeric antigen receptor (CAR) T cell, which exhibits reactivity across cells expressing a range of endogenous NECTIN4, with enhanced activity in high expressors. We demonstrate that the PPARγ pathway, critical for luminal differentiation, transcriptionally controls NECTIN4, and that the PPARγ agonist rosiglitazone primes and augments NECTIN4 expression, thereby increasing sensitivity to NECTIN4-CAR T cell-mediated killing.
View Article and Find Full Text PDFUrol Oncol
September 2025
Nutritional, Genes and Human Disease Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh. Electronic address:
Background: Understanding the mutational landscape is critical for elucidating the molecular mechanisms driving cancer progression. This study aimed to profile somatic mutations in bladder cancer patients (N=7) from Bangladesh to provide insights into the genetic alterations underlying this malignancy.
Methods: We performed targeted sequencing of 50 oncogenes and tumor suppressor genes using the Ion AmpliSeq Cancer Hotspot Panel v2 on tumor and matched blood samples from seven bladder cancer patients.
Eur J Med Chem
September 2025
Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Pharmaceutical Sciences, Health Science Center, Hunan Normal University, Changsha, 410013, Hunan, China. Electronic address:
Transl Oncol
September 2025
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address:
Bladder cancer (BC) remains a common malignancy, with muscle-invasive bladder cancer (MIBC) comprising 20 % of cases and a poor 5-year survival rate of ∼50 %. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy is the standard treatment for locally advanced disease, NAC is limited by toxicity and non-response in many patients. Predictive biomarkers are urgently needed to guide treatment decisions.
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