Bladder cancer is characterized by a high recurrence rate and aggressive behavior, with frequent emergence of chemoresistance. Current treatments such as surgery, chemotherapy, and immunotherapy have limited efficacy, underscoring the urgent need for effective early diagnostic biomarkers and novel targeted therapies.

Background: The benefits of first-line, cisplatin-based chemotherapy for muscle-invasive bladder cancer are limited due to intrinsic or acquired resistance to cisplatin. Increasing evidence has revealed the implication of cancer stem cells in the development of chemoresistance. However, the underlying molecular mechanisms remain to be elucidated. This study investigates the role of LASS2, a ceramide synthase, in regulating Wnt/β-catenin signaling in a subset of stem-like bladder cancer cells and explores strategies to sensitize bladder cancer to cisplatin treatment. Methods: Data from cohorts of our center and published datasets were used to evaluate the clinical characteristics of LASS2. Flow cytometry was used to sort and analyze bladder cancer stem cells (BCSCs). Tumor sphere formation, soft agar colony formation assay, EdU assay, apoptosis analysis, cell viability, and cisplatin sensitivity assay were used to investigate the functional roles of LASS2. Immunofluorescence, immunoblotting, coimmunoprecipitation, LC–MS, PCR array, luciferase reporter assays, pathway reporter array, chromatin immunoprecipitation, gain-of-function, and loss-of-function approaches were used to investigate the underlying mechanisms. Cell- and patient-derived xenograft models were used to investigate the effect of LASS2 overexpression and a combination of XAV939 on cisplatin sensitization and tumor growth. Results: Patients with low expression of LASS2 have a poorer response to cisplatin-based chemotherapy. Loss of LASS2 confers a stem-like phenotype and contributes to cisplatin resistance. Overexpression of LASS2 results in inhibition of self-renewal ability of BCSCs and increased their sensitivity to cisplatin. Mechanistically, LASS2 inhibits PP2A activity and dissociates PP2A from β-catenin, preventing the dephosphorylation of β-catenin and leading to the accumulation of cytosolic phospho-β-catenin, which decreases the transcription of the downstream genes ABCC2 and CD44 in BCSCs. Overexpression of LASS2 combined with a tankyrase inhibitor (XAV939) synergistically inhibits tumor growth and restores cisplatin sensitivity. Conclusions: Targeting the LASS2 and β-catenin pathways may be an effective strategy to overcome cisplatin resistance and inhibit tumor growth in bladder cancer patients.

Advanced prostate cancer, particularly castration-resistant disease, remains challenging to treat due to intratumoral heterogeneity, immune exclusion, and a suppressive tumor microenvironment. Within this ecosystem, cancer-associated fibroblasts shape tumor–stroma communication, but their marked heterogeneity and plasticity complicate classification and make indiscriminate fibroblast depletion potentially ineffective or even harmful. This review summarizes recent progress in fibroblast origins, functional subtypes, and fibroblast-driven mechanisms that promote tumor progression and therapy resistance, as well as emerging therapeutic opportunities in prostate cancer. We conducted a structured literature search of PubMed, ScienceDirect, and major publisher platforms (including Nature and SpringerLink) from database inception to 15 February 2025, supplemented by targeted manual screening of reference lists. Evidence from single-cell/spatial-omics and mechanistic studies indicates that prostate tumors contain multiple fibroblast programs that occupy distinct niches yet can interconvert. Across these studies, it was found that these fibroblasts contribute to immune suppression, extracellular matrix remodeling and stromal barrier formation, angiogenesis, and metabolic support, collectively limiting drug penetration and reinforcing immune evasion; therapeutic pressure can further rewire fibroblast states and resistance-associated signaling. Overall, the literature supports a shift toward function- and subtype-directed intervention rather than “one-size-fits-all” targeting, with promising directions including precision targeting and reversible reprogramming, rational combination strategies, and localized delivery approaches that reduce stromal barriers while preserving tissue homeostasis in high-risk and treatment-refractory prostate cancer.

Bladder cancer (BC) is a prevalent urinary malignancy characterized by high recurrence rates and suboptimal long-term outcomes from traditional treatments such as surgery, chemotherapy, and radiotherapy. T-cell-based immunotherapy has emerged as a promising approach, harnessing T cells’ capacity to target and destroy tumor cells, yet it faces challenges from the immunosuppressive tumor microenvironment (TME), immune evasion, and T-cell exhaustion. Nanomaterials offer innovative solutions by enabling targeted delivery of antigens, checkpoint inhibitors, and immunomodulators; remodeling the TME through metabolic interventions (eg, hypoxia alleviation and adenosine reduction); and enhancing T-cell infiltration and persistence with stimulus-responsive systems like pH-sensitive nanoparticles and biomimetic vesicles. This review systematically examines nanomaterial integration to amplify T-cell-mediated immunity in BC, covering T-cell origins, differentiation (eg, CD8+ cytotoxic and CD4+ helper subsets), roles in the TME, and exhaustion mechanisms driven by factors like PD-1 and TOX. We discuss key strategies including direct immune enhancement via immunogenic cell death induction, metabolic reprogramming to optimize T-cell function, and sustained activation for improved persistence. In conclusion, these nanomaterial-enhanced therapies address critical barriers, promoting precise and synergistic immune responses. Future prospects highlight AI-driven designs, personalized medicine, and clinical translation to tackle heterogeneity, biosafety, and resistance for durable BC remission.

Non-muscle invasive bladder cancer (NMIBC) has a high rate of postoperative recurrence and the efficacy of existing clinical prediction models is limited. This study aimed to combine multiparametric magnetic resonance imaging (mp-MRI) radiomic features with clinical characteristics to construct a machine learning model for accurately predicting the risk of recurrence within 2 years postoperatively in NMIBC patients. Retrospectively including 183 NMIBC patients (57 in the recurrence group, 126 in the non-recurrence group), radiomic features from mp-MRI imaging (T2W, ADC, and enhancement sequences) were extracted. Through LASSO selection, 4 key imaging features (MajorAxisLength, SZNN, S/V, Skewness) and 6 clinical features based on the EAU 2021 risk stratification were identified to constitute the clinical-imaging dataset. Through comparison with 10 machine learning models, Support Vector Machine (SVM) performed the best (training set AUC = 0.973, validation set AUC = 0.891), with external independent validation (108 cases) showing AUCs of 0.88 and 0.87, demonstrating good generalization ability. A bar chart integrating radiomics score (Rad-Score) with clinical features provides an intuitive prognostic tool. The study indicates that the clinical-imaging radiomics model based on SVM significantly enhances the efficacy of NMIBC recurrence prediction, addressing the shortcomings of traditional risk assessment and offering a reliable basis for personalized postoperative management. Study limitations include the retrospective design and the absence of molecular biomarkers, necessitating future multicenter prospective validation.

Background Tobacco is a significant risk factor for bladder cancer, with notable disparities in smoking rates and cancer prevalence between sex. Our objective is to assess the sex- and age-specific burden of bladder cancer attributable to smoking in China from 1990 to 2021, and predict its future trends over the next 15 years using GBD study data. Methods All data were extracted from the 2021 GBD study, utilizing metrics such as mortality rates, disability-adjusted life years (DALYs), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) to describe the burden of smoking-attributable bladder cancer in China. We employed joinpoint and age-period-cohort (APC) analysis methods to elucidate the epidemiological characteristics of bladder cancer. Frontier analysis was used to visually demonstrate the potential for burden reduction based on the development level of each country or region. We applied the ARIMA model to fit and predict the future burden of smoking-attributable bladder cancer in China for the next 15 years. Results From 1990 to 2021, the number of deaths and DALYs due to smoking-attributable bladder cancer in China significantly increased. However, ASMR and ASDR decreased for both sexs but males experiencing a higher burden. Population aging drove the decline in ASMR and ASDR, despite rising absolute deaths and DALYs. Joinpoint regression yielded average annual percentage changes (AAPC) of − 1.23 for ASMR and − 1.38 for ASDR, with the rate of change being lower in males than in females. The impact of age, period, and cohort on mortality rates varied. There was a slight increase in relative health inequality in the bladder cancer burden among countries of different income levels. By 2036, ASDR and ASMR for smoking-related bladder cancer in China are expected to continue decreasing, with this trend being more pronounced in males. Conclusion Over the past three decades, the number of deaths and DALYs due to smoking-related bladder cancer in China has significantly increased across different sexs and age groups, while ASMR and ASDR have shown a declining trend, reflecting certain public health progress. This trend is especially evident among males and is primarily driven by population aging and demographic effects. The inequality among countries of different income levels has slightly increased. The burden of smoking-related bladder cancer in China is projected to continue declining by 2036, particularly among males. Therefore, precise prevention and intervention strategies targeting different sexs and age groups are essential to further alleviate the public health burden of smoking-related bladder cancer.