Journal of Cancer最新文献

{"title":"Molecular mechanism and potential role of mitophagy in breast cancer.","authors":"Xin Yang, Youqin Zeng, Ling Zhang, Yuting Ye, Siyu Chen, Changyou Wei, Ping Leng","doi":"10.7150/jca.140132","DOIUrl":"10.7150/jca.140132","url":null,"abstract":"<p><p>Breast cancer remains the most commonly diagnosed malignancy among women worldwide and a leading cause of cancer related mortality in this population. Mitochondrial dysfunction is increasingly recognized as a hallmark of breast cancer, contributing to tumor initiation, progression, and therapeutic resistance. Mitophagy, a selective form of autophagy that eliminates damaged or dysfunctional mitochondria, is essential for maintaining cellular and mitochondrial homeostasis. Accumulating evidence indicates that mitophagy plays a context dependent role in breast cancer. Impaired mitophagy permits the accumulation of damaged mitochondria and promotes tumor growth, migration, and invasion, whereas appropriately activated mitophagy removes damaged mitochondria and suppresses tumor progression. This review synthesizes the molecular mechanisms of mitophagy, its crosstalk with ferroptosis, and its context dependent roles in breast cancer development, with the aim of offering therapeutic insights that may inform breast cancer treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 10","pages":"1808-1820"},"PeriodicalIF":3.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A candidate PPARγ to GPX4 axis in ferroptosis suppression and platinum resistance in bladder cancer: evidence appraisal and a testable research agenda.","authors":"Shenjuan Li, Hongwei Peng, Gang Li, Ziyu Wan, Mengxue Yu, Sheng Tu, Fangjin Chen, Lingao Ju, Gang Wang, Kaiyu Qian, Yu Xiao, Zilin Xu","doi":"10.7150/jca.139186","DOIUrl":"10.7150/jca.139186","url":null,"abstract":"<p><p>Cytotoxic chemotherapy no longer holds an uncontested place in the treatment of muscle-invasive bladder cancer, although platinum-based therapy remains relevant in selected perioperative, bladder-preservation, upper-tract, and salvage settings. Mechanisms of platinum resistance therefore retain clinical importance. Ferroptosis, an iron-dependent form of regulated cell death constrained by glutathione peroxidase 4 (GPX4), has been implicated in treatment tolerance and drug-tolerant persister states. Here, we provide a narrative evidence appraisal of peroxisome proliferator-activated receptor gamma (PPARγ) as a candidate upstream regulator of GPX4-dependent ferroptosis resistance in bladder cancer. Two mechanistic arms are considered. The first proposes transcriptional regulation of GPX4 by PPARγ; however, positive regulation in bladder cancer is supported only by expression co-variation and in silico motif prediction, while evidence from another cellular context indicates that the direction of PPARγ-GPX4 regulation can be reversed. The second proposes that reduced SIRT1 activity could alter GPX4 acetylation and thereby influence its post-translational regulation. Although GPX4 acetylation has been directly demonstrated in non-urothelial systems, GPX4 has not been established as a SIRT1 substrate, and SIRT1-dependent control of GPX4 ubiquitination or turnover remains untested. We therefore present the PPARγ-GPX4 relationship as a context-dependent, testable hypothesis rather than an established \"dual-lock\" mechanism, and outline the experiments required to establish transcriptional directionality, post-translational regulation, ferroptosis dependence, and platinum sensitization in urothelial models.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 10","pages":"1797-1807"},"PeriodicalIF":3.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EfficientNetB5-Based Deep Learning for Automated Cancer Detection in Tissue Microarray Images.","authors":"Kuo-Wang Tsai, Bach-Tung Pham, Ching-Feng Cheng, Chun-Fan Lung, Wenny Ramadha Putri, Farchan Raswa, Jia-Ching Wang, Yi-Chiung Hsu","doi":"10.7150/jca.139302","DOIUrl":"10.7150/jca.139302","url":null,"abstract":"<p><strong>Background: </strong>Tissue microarray (TMA) technology is pivotal in cancer research, enabling simultaneous analysis of multiple samples on a single slide. Manual analysis of TMA images remains time-consuming and subjective. This study aimed to develop a robust deep learning model to automate TMA image analysis, enhance accuracy, and support cancer diagnosis.</p><p><strong>Methods: </strong>We utilized the EfficientNetB5 deep learning architecture to classify TMA images from the DigitalSlide01 v1_1M01 dataset, comprising breast cancer, Upper Tract Urothelial Carcinoma (UTUC), and gastric cancer samples. Data augmentation methods, including Mix-Up and Cut-Mix, were employed to improve generalization. Preprocessing involved Otsu thresholding and smart bounding box cropping. The model was trained over 80 epochs using the Adam optimizer, a learning rate scheduler, and categorical cross-entropy loss. Performance was evaluated using 10-fold cross-validation and a separate test set, with accuracy, precision, recall, and F1-score as the primary metrics. Performance was further examined using physical-array-held-out and sample-level analyses.</p><p><strong>Results: </strong>Across the 10 cross-validation validation folds, mean accuracy and F1-score were 85.93% and 82.78%, respectively. Across the separate test-set evaluations by the ten fold-specific models, mean accuracy and F1-score were 80.08% and 75.13%, respectively. In the sample-level analysis, a 10-model mean-probability ensemble achieved 87.80% accuracy and 78.18% macro F1-score on the 246-core test subset. Cancer precision was 100.00% in the reported ensemble analysis, indicating that no Normal or Others samples were observed among samples predicted as Cancer; this does not imply that all Cancer samples were detected.</p><p><strong>Conclusions: </strong>The EfficientNetB5-based framework showed useful aggregate classification performance. These findings support the feasibility of automated TMA image classification and emphasize the need for source-balanced external multicenter validation before broader clinical application.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 10","pages":"1821-1828"},"PeriodicalIF":3.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Per-patient Comparison of [⁶⁸Ga]-FAPI-46 Versus [¹⁸F]FDG as PET Tracers in ER-positive Breast Cancer: Study Design of a Single-centre Prospective Study.","authors":"Melissa Lenaerts, Lisa E H W Duijx, Felix M Mottaghy, Matthias Bauwens, Robin M J M van Geel, Vivianne C G Tjan-Heijnen, Philipp Backhaus, Loes F S Kooreman, Patty J Nelemans, Marjolein L Smidt, Joachim E Wildberger, Thiemo J A van Nijnatten","doi":"10.7150/jca.138448","DOIUrl":"10.7150/jca.138448","url":null,"abstract":"<p><p><b>Introduction.</b> [¹⁸F]FDG can be considered as PET tracer to determine whole-body staging in patients with locally advanced (LABC), metastatic, and recurrent breast cancer. Yet, previous studies demonstrated a lower amount of metabolic accumulation on [¹⁸F]FDG PET in case of oestrogen receptor (ER)-positive breast cancer. Consequently, given the lower metabolic accumulation, patients with ER-positive breast cancer might be at risk for underdiagnosis according to [¹⁸F]FDG PET. A novel PET tracer, [⁶⁸Ga]-fibroblast activation protein inhibitor (FAPI)-46, has shown promising results in breast cancer (re)staging. This single-centre prospective pilot study aims to explore the relative diagnostic accuracy of [⁶⁸Ga]-FAPI-46 compared to [¹⁸F]FDG in patients with ER-positive breast cancer and will provide the required information to support sample size calculation for a future validation study. <b>Methods.</b> In this study, 20 patients with ER-positive LABC, metastatic, or recurrent breast cancer will undergo the standard [¹⁸F]FDG PET exam and a [⁶⁸Ga]-FAPI-46 PET/CT and [⁶⁸Ga]-FAPI-46 PET/MRI exam. Histopathological confirmation will be obtained in cases of discordant or concordant (double-positive) findings, depending on clinical relevance and technical feasibility. The study will provide preliminary estimates of the relative accuracy of [⁶⁸Ga]-FAPI-46 PET when compared to [¹⁸F]FDG PET as well as the proportion of discordant findings and patients in whom a biopsy is feasible. <b>Conclusions.</b> The present single-centre prospective pilot study will characterize the potential of [⁶⁸Ga]-FAPI-46 PET to identify additional lesions not detected on a [¹⁸F]FDG PET exam in patients with ER-positive breast cancer to estimate an adequate sample size for a future validation study. <b>Trial registration.</b> This study was registered prospectively on ClinicalTrials.gov. Trial registration number: NCT06335069; Register date: 28 March 2024.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 10","pages":"1767-1772"},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiation-induced SLAMF1 reconfigures the SLAM family receptors landscape in triple-negative breast cancer cells.","authors":"Kyung-Hee Song, Jeong-In Park, Seung-Youn Jung, Hong-Jun Park, Jiyeon Ahn, Sang-Gu Hwang, Dae-Seog Lim, Jie-Young Song","doi":"10.7150/jca.137668","DOIUrl":"10.7150/jca.137668","url":null,"abstract":"<p><p>Radiation therapy is a powerful immunomodulator capable of transforming the tumor microenvironment (TME). Signaling Lymphocytic Activation Molecule Family Member 1 (SLAMF1) is a cell surface receptor involved in various immune functions and cancer progression by regulating interactions with the immune microenvironment. However, the specific role of radiation in modulating the SLAM family within tumor cells remained poorly understood. Ionizing radiation markedly increased the expression of SLAM family, including SLAMF1, and other immune checkpoints in three triple-negative breast cancer (TNBC) cell lines by flow cytometry analysis. Furthermore, dual immunofluorescence staining of breast cancer patient tissues confirmed that SLAMF1 is localized to tumor site independently of immune cells. Interestingly, SLAMF1 overexpression in TNBC cells distinctively reconfigures the expression of SLAMF2 and SLAMF5, both linked to immunosuppressive signaling. These findings suggest a potential mechanism where radiation-induced SLAMF1 influences tumor immunogenicity by remodeling the inhibitory SLAM receptors landscape, potentially rendering tumor cells more susceptible to immune-mediated attack. As the first study to demonstrate endogenous SLAMF1 as a novel radiation-responsive factor in breast cancer, these results provide key insights for developing combined radiotherapy and immunotherapy strategies for TNBC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 10","pages":"1773-1782"},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of neuro-related genes in colorectal cancer and their potential implications for immunotherapy.","authors":"Huantong Wu, Weihua Liu, Shengtao Zhu","doi":"10.7150/jca.136690","DOIUrl":"10.7150/jca.136690","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a leading cause of cancer mortality. This study investigates the prognostic and immunological role of neural-related genes (NRGs) in CRC. Using The Cancer Genome Atlas (TCGA) data, a four-gene signature (POU4F1, KLC3, ATP2A1, CALB2) was constructed via Cox and least absolute shrinkage and selection operator (LASSO) regression. This signature independently predicted patient survival. High-risk patients showed enrichment in cytokine signaling and oxidative phosphorylation. Importantly, CALB2 expression correlated with increased infiltration of NKT and central memory CD4+ T cells, while high-risk scores were associated with greater potential for immune evasion. Single-cell analysis revealed epithelial cells as the primary source of these NRGs. This NRG-based signature provides a novel biomarker for prognosis and immunotherapy optimization in CRC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 10","pages":"1744-1766"},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes from Cancer-associated Fibroblasts Orchestrate Lung Metastasis of Breast Cancer via LncRNA LMAEP.","authors":"Liyan Lao, Huiping Chen, Huiyi Zeng, Penghan Huang, Yufei Chen, Jianing Chen, Wei Wu, Wenfeng Zeng","doi":"10.7150/jca.139124","DOIUrl":"10.7150/jca.139124","url":null,"abstract":"<p><p>Lung metastasis is a leading cause of patient mortality in breast cancer. Cancer-associated fibroblasts (CAFs), the most abundant stromal cells within the tumor microenvironment, are closely implicated in pulmonary metastasis. Nevertheless, the mechanism underlying CAF-mediated metastasis remains elusive. We found that density of CAFs in primary tumors showed no significant difference in patients with or without lung metastasis. However, CAFs of breast cancer patients with lung metastasis (termed lung metastasis-associated fibroblasts, LMAFs) exhibited immense competence in inducing epithelial-mesenchymal transition (EMT), invasion and proliferation of tumor cells relative to non-metastatic CAFs. LMAF-derived exosomes were sufficient to confer the pro-metastatic phenotype to tumor cells. LncRNA microarray screening identified LMAEP (Lung Metastasis-Associated EMT Promoter) as a lncRNA specifically enriched in LMAF-derived exosomes. Knockdown of LMAEP abrogated the capacity of LMAFs to induce cancer cell EMT, invasion and proliferation. Targeting of lncRNA LMAEP tremendously suppressed tumor growth and lung metastasis of breast cancer <i>in vivo</i>. These findings identify LMAEP as a critical metastasis-inducing mediator of CAFs, positioning it as a potential biomarker for risk prediction and early detection of lung metastasis. Furthermore, targeting exosomal lncRNA LMAEP represents a promising therapeutic strategy for restraining pulmonary metastasis of breast cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 10","pages":"1783-1796"},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bevacizumab or Aflibercept in Combination with Second-Line FOLFIRI after Progression on FOLFOX Plus Bevacizumab in Metastatic Colorectal Cancer: A Comparative Study.","authors":"Okan Aydin, Sermin Dinc Sonusen, Asli Buyukkuscu, Seyyit Bayram Sahin, Serhat Kalkan, Ahmet Emin Ozturk, Mert Erciyestepe, Fatih Atalah, Zehra Sucuoglu Isleyen, Emir Celik, Kayhan Erturk, Muhammed Mustafa Atci","doi":"10.7150/jca.138530","DOIUrl":"10.7150/jca.138530","url":null,"abstract":"<p><strong>Background: </strong>The optimal anti-angiogenic strategy in the second-line treatment of metastatic colorectal cancer (mCRC) after progression on first-line FOLFOX plus bevacizumab remains unclear. We aimed to compare the efficacy and safety of FOLFIRI combined with bevacizumab or aflibercept in this well-defined clinical setting.</p><p><strong>Methods: </strong>In this retrospective single-center study, 152 patients with mCRC who progressed after at least four cycles of first-line FOLFOX plus bevacizumab were included. Of these, 92 patients received FOLFIRI plus bevacizumab and 60 received FOLFIRI plus aflibercept as second-line therapy. Stabilized inverse probability of treatment weighting (IPTW) was applied to account for baseline differences between treatment groups. PFS and OS were evaluated using IPTW-weighted Kaplan-Meier and Cox regression analyses.</p><p><strong>Results: </strong>No statistically significant difference was observed between the bevacizumab and aflibercept groups for PFS (HR: 1.302, 95% CI: 0.929-1.825, p=0.125) or OS (HR: 1.212, 95% CI: 0.846-1.736, p=0.295) in the IPTW-weighted analyses. Treatment type was not independently associated with PFS or OS in multivariate analyses. Grade 3-4 toxicities were observed in both groups, with neutropenia being the most common; thrombocytopenia and neutropenia were numerically more frequent in the aflibercept group.</p><p><strong>Conclusion: </strong>No statistically significant differences in efficacy were observed between FOLFIRI plus bevacizumab and FOLFIRI plus aflibercept in patients with mCRC progressing after first-line FOLFOX plus bevacizumab. Both strategies represent reasonable second-line options in this setting, highlighting the need for prospective studies to define the optimal sequencing of anti-angiogenic therapies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 10","pages":"1733-1743"},"PeriodicalIF":3.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Separability of histopathology foundation model embeddings of stimulated Raman histology images for lung carcinoma subtyping.","authors":"Karl-Moritz Schröder, Uyen-Thao Le, Birte Ohm, Till Nicke, Martin Peter Pichotka, Martin Werner, Jürgen Beck, Jakob Straehle, Rainer Schmelzeisen, Leonard Brandenburg, Peter Bronsert, Andreas Weber-Steinhilber","doi":"10.7150/jca.135384","DOIUrl":"10.7150/jca.135384","url":null,"abstract":"<p><p>Histopathology foundation models trained on hematoxylin and eosin (H&E) whole-slide images have recently emerged as versatile encoders for downstream diagnostic tasks, but their transferability to out-of-domain imaging modalities such as stimulated Raman histology (SRH) is unknown. Here, we retrospectively evaluated whether embeddings from histopathology foundation models enable intraoperative SRH-based classification of lung cancer patients into (i) non-small cell lung cancer (NSCLC) versus pulmonary metastasis (MET) and (ii) adenocarcinoma (AC) versus squamous cell carcinoma (SCC). For NSCLC versus MET, embeddings from histopathology foundation models showed separability in a range comparable to ResNet50. In contrast, for AC versus SCC, histopathology foundation models showed a tendency to outperform ResNet50, although without statistical significance. Overall performance remained too low to support clinical deployment. Nonetheless, our results indicate that histopathology foundation models could transfer discriminative representations to SRH images for specific intraoperative subtyping tasks.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 10","pages":"1698-1708"},"PeriodicalIF":3.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urine-derived induced pluripotent stem cells for non-invasive diagnosis of bladder cancer.","authors":"Yuan Zhu, Jia Shang, Xin Zhang, Sheng Tu, Gang Li, Shenjuan Li, Hongwei Peng, Haoli Ma, Fangjin Chen, Wan Xiang, Cong Zou, Yu Xiao, Zilin Xu, Kaiyu Qian, Gang Wang","doi":"10.7150/jca.138160","DOIUrl":"10.7150/jca.138160","url":null,"abstract":"<p><p>Bladder cancer (BLCA) remains one of the most prevalent and costly malignancies worldwide, largely owing to its high recurrence rate and the invasive nature of conventional surveillance modalities. Induced pluripotent stem cell (iPSC) technology offers a new framework for disease modeling and, potentially, precision diagnostics. Urine provides a non-invasive, renewable source of exfoliated urothelial and renal epithelial cells amenable to direct reprogramming. Here, we review the biological rationale, reprogramming methodology, and diagnostic potential of urine-derived iPSCs (UDiPSCs) in the context of BLCA detection and monitoring. We further discuss the genomic fidelity of UDiPSCs, the extent to which they may retain patient-relevant oncogenic features, their integration with multi-omics platforms, and the translational challenges that must be resolved before clinical deployment. Because reprogramming resets the somatic epigenome and transcriptome, we propose a tiered strategy in which methylation is assessed in parental urinary cells, genomic variants in reprogrammed clones, and transcriptional phenotypes in differentiated derivatives. Compared with urinary tumor DNA methylation panels and urine-derived tumor organoids, which currently exceed cell-based reprogramming approaches in accuracy, cost-effectiveness, and turnaround, UDiPSCs offer a distinct niche: interrogating rare, non-tumorigenic, field-altered urothelial cells that are diluted in bulk urinary DNA and do not form organoids. Collectively, UDiPSC-based platforms provide a plausible route toward non-invasive, personalized BLCA biomarkers, although clinical utility remains to be established through prospective validation.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 10","pages":"1720-1732"},"PeriodicalIF":3.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}