Technology in Cancer Research & Treatment最新文献

{"title":"Retraction: Bifidobacteria Expressing Tumstatin Protein for Antitumor Therapy in Tumor-Bearing Mice.","authors":"","doi":"10.1177/15330338251412609","DOIUrl":"10.1177/15330338251412609","url":null,"abstract":"","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"25 ","pages":"15330338251412609"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Different Maintenance Treatment Options for Newly Diagnosed <i>BRCA</i>wt Advanced Ovarian Cancer: A Retrospective Cohort Analysis.","authors":"Xi Chen, Chenyan Fang, Yanglong Guo, Yingli Zhang","doi":"10.1177/15330338261416162","DOIUrl":"10.1177/15330338261416162","url":null,"abstract":"<p><p>IntroductionNiraparib and bevacizumab are two principal maintenance therapies for newly diagnosed advanced ovarian cancer (AOC) patients with <i>BRCA</i> wild-type (<i>BRCA</i>wt) status, regardless of homologous recombination deficiency (HRD). In China, however, a considerable proportion of <i>BRCA</i>wt patients have unknown or untested HRD status, complicating treatment selection.MethodsTo evaluate and compare the efficacy of niraparib and bevacizumab as maintenance therapy for <i>BRCA</i>wt AOC, we conducted a retrospective cohort study using real-world clinical data. Descriptive statistics were used to summarize clinical and demographic characteristics. Progression-free survival (PFS) was estimated using Kaplan-Meier analysis and compared using a stratified Cox proportional hazards model. A multivariable Cox regression was performed to adjust for potential confounding variables. Exploratory subgroup analyses were conducted, and propensity score matching (PSM) was applied as a sensitivity analysis.ResultsA total of 94 patients were included, with 51 receiving niraparib and 43 receiving bevacizumab. The median PFS was not reached in the niraparib group versus 13.77 months (95% CI, 4.12-23.41) in the bevacizumab group (HR = 0.240, 95% CI, 0.128-0.451; <i>P</i> < .001). After covariate adjustment, the median PFS was 19.55 months (95% CI, 9.40-NA) with niraparib and 8.64 months (95% CI, 4.53-NA) with bevacizumab, with an adjusted HR of 0.282 (95% CI, 0.136-0.587; <i>P</i> = .001). In the PSM sensitivity analysis, the median PFS was not reached (95% CI, 19.55-NR) in the niraparib group and was 18.33 months (95% CI, 8.90-25.26) in the bevacizumab group (HR = 0.360, 95% CI, 0.176-0.736; <i>P</i> = .005).ConclusionThis analysis suggests that niraparib may provide a progression-free survival advantage compared with bevacizumab in <i>BRCA</i>wt AOC patients, with both regimens appearing to be generally well tolerated in the real-world setting. These findings offer preliminary reference value for maintenance treatment selection in patients with newly diagnosed <i>BRCA</i>wt AOC.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"25 ","pages":"15330338261416162"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12873068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of a Non-Clamping Sutureless Technique Combined with Radiofrequency Ultrasound Scalpel in Laparoscopic Nephron-Sparing Surgery for T1 Renal Cell Carcinoma: A Retrospective Cohort Study.","authors":"Shenglan Yuan, Shenghan Xu, Yi Mu, Bangwei Che, Jiancheng Zhai, Kaifa Tang","doi":"10.1177/15330338261418622","DOIUrl":"10.1177/15330338261418622","url":null,"abstract":"<p><p>ObjectiveThis study aimed to assess renal cell carcinoma (RCC) complexity using the R.E.N.A.L. nephrometry score and evaluate the feasibility and safety of the non-clamping sutureless technique combined with a radiofrequency ultrasound scalpel (RFUS) for low-complexity RCC.MethodsThis retrospective, multi-center cohort study categorized patients into three groups: Group I (suture laparoscopic partial nephrectomy [LPN] with clamping renal artery), Group II (sutureless LPN without renal artery clamping, combined with monopolar electrocoagulation), and Group Ⅲ (sutureless laparoscopic nephron-sparing surgery [LNSS] without renal artery clamping combined with RFUS). Key outcomes included operative time, intraoperative blood loss, postoperative hospital stays, serum creatinine (Scr) levels, and the estimated glomerular filtration rate (eGFR) of the affected kidney. Post hoc power analysis was used to evaluate eGFR variation across groups, and a multiple linear regression model was employed to analyze factors influencing postoperative eGFR alterations.ResultsThe study included 60 patients with exophytic and low-complexity RCC. Blood loss in Group III was comparable to that in Group I but less than that in Group II (<i>P</i> = 0.035). Operative time and postoperative hospital stays were significantly shorter in Group III than in the other groups (<i>P</i> < 0.01). A statistically significant increase in Scr levels was observed during the early postoperative period, continuing through the 6-month follow-up assessment compared with preoperative levels (<i>P</i> < 0.01). The 6-month postoperative eGFR of the affected kidney in Group III was significantly higher than that in the other groups (<i>P</i> < 0.01). The decrease in preoperative and 6-month postoperative eGFR values was greatest in Group I (<i>P</i> < 0.01), followed closely by Group II (<i>P</i> < 0.01), while no significant reduction was observed in Group III. The post hoc power analysis revealed high detection power (0.912 or 1.0). Warm ischemia time emerged as the sole significant eGFR predictor (<i>R²</i> = 0.814, <i>P</i> < 0.05).ConclusionThe non-clamping sutureless technique combined with RFUS for RCC effectively alleviates renal ischemia-reperfusion injury, offering superior renal function protection while achieving comparable oncological outcomes.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"25 ","pages":"15330338261418622"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation of Novel Fully Human Single-Domain Antibodies Targeting GUCY2C from a Heavy-Chain-Only Transgenic Mouse Platform.","authors":"Pingxia Zhu, Lei He, Xiaoming Du, Pengsha Pang, Zhihua Ji, Yanyu Yang, Fengqi Cao, Quanjun Wang","doi":"10.1177/15330338261473054","DOIUrl":"10.1177/15330338261473054","url":null,"abstract":"<p><p>IntroductionTraditional natural single-domain antibodies(sdAbs) are primarily derived from camelids and sharks. However, the large size and slow reproduction of these species limit their widespread application in antibody development. In this study, we employed a fully human heavy-chain-only antibody mouse ( huNano mouse ) platform and a rapid, efficient preparation process to successfully develop fully human heavy-chain-only antibodies(HcAbs) targeting the tumor antigen guanylyl cyclase C (GC-C). These sdAbs provide high-quality candidate molecules for subsequent GC-C-based CAR-T therapy and bispecific antibody drug development.MethodsFully huNano mice were immunized with GC-C recombinant protein. SdAb sequences specifically binding to GC-C were selected via phage display technology and subsequently cloned into mammalian expression vectors for expression and purification. The binding activity, affinity, thermal stability, and monomeric dispersion of the antibodies were systematically evaluated using various methods, including ELISA, flow cytometry (FACS), biolayer interferometry (BLI), and size-exclusion chromatography (SEC-HPLC).ResultsMultiple sdAbs with specific recognition of GC-C were successfully obtained and exhibited strong binding affinities. After one-step purification, the monomeric purity of most antibodies exceeded 95%, with aggregate content below 5%. The nanobodies exhibited good thermal stability, with melting temperature (Tm) and aggregation onset temperature (Tagg) both falling within the range of 60-68 °C, demonstrating excellent drug development potential.ConclusionThese results validate the capability of the huNano mouse platform to efficiently produce high-quality, fully human sdAbs.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"25 ","pages":"15330338261473054"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Call for a Collaborative Framework for Automation in Adaptive Radiotherapy.","authors":"Songye Cui, Maria F Chan","doi":"10.1177/15330338261449016","DOIUrl":"10.1177/15330338261449016","url":null,"abstract":"<p><p>Adaptive radiotherapy (ART) has been shown to improve geometric and dosimetric accuracy, with emerging evidence for clinical benefit, but it remains resource-intensive and lacks scalability. This limitation arises from multiple factors, including the complexity of current systems, the closed and proprietary nature of radiotherapy platforms, and the need for human oversight driven in part by clinical risk considerations. Historically, major advances in radiotherapy-from Intensity-Modulated Radiation Therapy (IMRT) and Image-Guided Radiation Therapy (IGRT) to Magnetic Resonance-guided Radiotherapy (MRgRT) and Deep Learning in Radiotherapy (DLinRT) (particularly for auto-contouring)-have thrived through open collaboration and transparency. The community can accelerate ART innovation by returning to this model. Open-source initiatives such as Computational Environment for Radiotherapy Research (CERR), Open Knowledge-based Planning (OpenKBP), and matRad demonstrate how shared tools and methods improve reproducibility and drive scientific progress. The next critical step is to develop collaborative, structured frameworks that enable safe, secure interaction between academic and vendor systems-safeguarding intellectual property while fostering co-development and validation. Through structured transparency and shared accountability, the radiotherapy field can transform automation from a closed, non-transparent architecture into a collective learning ecosystem, ultimately extending the life-saving benefits of ART to more patients worldwide through openness, trust, and collective innovation.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"25 ","pages":"15330338261449016"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13153481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NeuroMorphFusion: A Neuro-Inspired Hybrid Learning Framework for Interpretable Deep Lesion Detection in IoT-Enabled Healthcare Systems.","authors":"Roseline Oluwaseun Ogundokun, Rotimi-Williams Bello, Pius Adewale Owolawi, Etienne A van Wyk, Chunling Tu","doi":"10.1177/15330338251391080","DOIUrl":"10.1177/15330338251391080","url":null,"abstract":"<p><p>IntroductionIntegrating deep learning within the Internet of Medical Things (IoMT) has revolutionized automated lesion detection in medical imaging. Yet, maintaining high diagnostic accuracy, interpretability and computational efficiency on resource-limited edge devices remains challenging. To address these gaps, we propose NeuroMorphFusion, a neuro-inspired hybrid framework that combines biologically plausible learning with mathematical modelling for interpretable and efficient lesion detection.MethodsNeuroMorphFusion integrates a lightweight ResNet18 backbone, a Spiking Neural Network (SNN) component to capture temporal dynamics, and a morphological attention mechanism that emphasizes structure-relevant regions in CT scans. The architecture employs a semi-supervised reinforcement learning strategy, where pseudo-label accuracy and the overlap between Grad-CAM visualizations and expert annotations define the reward, ensuring explainable updates under limited labelled data. Additionally, a genetic algorithm (GA) optimizes hyperparameters-learning rate, dropout rate, spiking time steps, and attention dimensionality - for domain generalization and reduced memory use. The optimization population is restricted to 20 individuals over 30 generations, converging within eight minutes on a Jetson Nano.ResultsA multi-objective optimization scheme balances lesion detection sensitivity, computational latency and explainability. Integrated SHAP and Grad-CAM visualizations enhance interpretability. Experimental evaluation on the IQ-OTHNCCD lung cancer CT dataset demonstrates that NeuroMorphFusion achieves 98.18% classification accuracy, outperforming VGG16, SqueezeNet, MobileNetV3, and ResNet18 in both transparency and efficiency.ConclusionNeuroMorphFusion effectively unites neuro-biological inspiration, mathematical interpretability, and edge-efficient computation for IoMT-based medical imaging. Its superior accuracy, explainability, and low-latency optimization highlight its potential for real-world clinical integration and scalable IoMT deployment.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"25 ","pages":"15330338251391080"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stacking Model-Based Preoperative Prediction of Lymphovascular Invasion in Lung Adenocarcinoma by Integrating Intratumoral Heterogeneity Score and Clinicoradiological Features: A Multicenter Study.","authors":"Yan Zhao, Zhichao Zuo, Yanping Wu, Wen Liu, Wanyin Qi, Jinqiu Deng, Yujie Feng","doi":"10.1177/15330338261470895","DOIUrl":"10.1177/15330338261470895","url":null,"abstract":"<p><p>IntroductionLymphovascular invasion (LVI) is associated with poor outcomes in lung adenocarcinoma, yet accurate preoperative prediction in clinical stage IA disease remains difficult. We aimed to develop and validate a multicenter ensemble machine-learning model that integrates intratumoral heterogeneity (ITH) score and clinicoradiological features for preoperative LVI prediction.MethodsIn this retrospective multicenter prediction-model development and external validation study, 1,527 patients with surgically confirmed stage IA lung adenocarcinoma from three tertiary centers were included. Patients from two centers formed the training cohort (n = 1,068), and patients from the third center formed the external validation cohort (n = 459). The intratumoral heterogeneity (ITH) score was quantified from preoperative computed tomography (CT) by integrating global and local pixel-distribution patterns. Ten base machine-learning algorithms and 31 stacking configurations were evaluated. Model performance was assessed using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score. SHapley Additive exPlanations (SHAP) were used for model interpretation and feature selection.ResultsThe XGBoost plus random forest stacking model ranked first overall according to the comprehensive score and achieved the best integrated diagnostic performance. In comparative analyses, the stacking model showed a more balanced diagnostic profile than the radiomics-only, ITH-only, and clinicoradiological-only models, with the highest overall mean performance, although the radiomics-only model showed a slightly higher AUC and sensitivity. SHAP analysis identified the ITH score as the dominant contributor to model output.ConclusionA stacking model integrating ITH score and clinicoradiological features enables reliable preoperative prediction of LVI in stage IA lung adenocarcinoma and may support individualized risk stratification and surgical planning.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"25 ","pages":"15330338261470895"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Day 14 Bone Marrow Biopsy in Acute Myeloid Leukemia Induction: The End of Story or Not Yet?","authors":"Mostafa F Mohammed Saleh, Abdulrahman Nasiri, Ahmed Abdrabou, Ali Alahmari, Syed O Ahmed, Ayman Saad, Mahmoud Aljurf","doi":"10.1177/15330338261429620","DOIUrl":"10.1177/15330338261429620","url":null,"abstract":"<p><p>The Day 14 bone marrow biopsy (D14 BMB) has historically been a key tool for early treatment response assessment in acute myeloid leukemia (AML), particularly following intensive chemotherapy. Traditionally, a blast count of <5% at D14 is associated with higher complete remission (CR) rates and improved overall survival (OS), while persistent disease often prompts re-induction therapy. However, emerging evidence suggests that while re-induction may increase CR rates, it does not consistently improve OS and is associated with significant morbidity. With the emergence of venetoclax-based and other targeted therapies, the traditional role of D14 BMB is being reconsidered, as these agents exhibit slower response kinetics, making later assessments and measurable residual disease (MRD) monitoring more reliable for treatment adaptation. This review critically examines the prognostic utility of D14 BMB in AML, its relevance across different treatment modalities, and its correlation with long-term outcomes. By synthesizing current evidence, we explore whether D14 BMB remains a valuable clinical tool or if a paradigm shift toward later assessments and MRD-guided decision-making is warranted in modern AML therapy.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"25 ","pages":"15330338261429620"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Decade of Interventional Radiotherapy (Brachytherapy): Progress, Challenges, and Future Prospects - A Bibliometric Analysis.","authors":"Federico Mastroleo, Ekaterina Milovanova, Stefano Durante, Federico Gagliardi, Mateusz Bilski, Bruno Fionda, Luca Tagliaferri, Alfonso Gomez-Iturriaga, Alina Sturdza, Alexandra Stewart, Mariana Borras-Osorio, Mark R Waddle, Giulia Marvaso, Andrea Vavassori, Łukasz Kuncman, Jacek Fijuth, Barbara Alicja Jereczek-Fossa","doi":"10.1177/15330338261415801","DOIUrl":"10.1177/15330338261415801","url":null,"abstract":"<p><p>BackgroundInterventional radiotherapy (IRT), also known as brachytherapy, has become a cornerstone of radiation oncology due to its ability to maximize therapeutic efficacy while minimizing side effects to surrounding tissues. This bibliometric analysis aims to examine the evolution of IRT over the past decade.Material and MethodsA string comprising IRT-related keywords was developed, and data were extracted from the Scopus database for English-language documents published between January 2014 and December 2024. The analysis was performed using Bibliometrix packageResultsA total of 15 755 documents from 2150 sources were analyzed, revealing an average annual growth rate of 1.03%. Publication trends were stable from 2014 to 2018, surged from 2019, and peaked in 2021, with subsequent levels remaining above pre-2019 figures. Original articles accounted for 72.7% of the literature, with key contributions from journals such as \"Brachytherapy\" and the \"Journal of Contemporary Brachytherapy\". The analysis highlighted strong collaborative networks, with significant input from North American and European institutions, and identified focal research themes including uterine cervical cancer and prostate brachytherapy. Emerging topics, such as deep learning, artificial intelligence, and personalized dosimetry, underscore the field's shift towards precision medicine.ConclusionsThe findings reflect IRT's dynamic research landscape and its growing integration into modern oncologic practice, emphasizing the need for continued interdisciplinary efforts and clinical trials to advance this minimally invasive treatment modality further.<b>Highlights</b>• A decade-long bibliometric analysis of 15 755 publications on interventional radiotherapy (IRT) reveals stable growth, with a notable surge in research activity post-2019.• Uterine, cervical, and prostate cancers remain the most studied clinical indications for IRT globally.• North American and European institutions dominate collaborative networks, reflecting the strength of transatlantic research partnerships.• Emerging research themes include artificial intelligence, deep learning, and personalized dosimetry-marking a transition toward precision oncology.• The field's evolving landscape highlights the increasing clinical and scientific significance of IRT in contemporary cancer care.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"25 ","pages":"15330338261415801"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Druggable Genome-Wide Mendelian Randomization Identifies Therapeutic Targets and DNA Methylation-Mediated Regulation in Urological Malignancies.","authors":"Taoen Li, Qiang Wei","doi":"10.1177/15330338261449014","DOIUrl":"10.1177/15330338261449014","url":null,"abstract":"<p><p>IntroductionUrological cancers, including prostate, renal, and bladder cancers, present significant challenges to human health, particularly for patients in advanced stages due to limited targeted therapy options, high drug resistance, and poor prognosis. This study seeks to systematically identify new therapeutic targets by integrating multi-omics data and elucidating their molecular mechanisms.MethodsOur methodology involved a multi-phase integrative approach to identify therapeutic targets in urological cancers. We conducted a transcriptome-wide Mendelian randomization (TWMR) analysis using the druggable genome. We used cis-expression quantitative trait loci (cis-eQTL) data from the eQTLGen consortium (N = 31,684) as exposures and GWAS summary statistics from FinnGen R11 and Open GWAS as outcomes. Significant genes were identified through Bonferroni correction, followed by colocalization analysis to assess shared genetic effects between risk SNPs and gene expression. Summary-data-based MR (SMR) analysis was carried out using eQTLGen data. Validation of potential targets included drug prediction using DSigDB and molecular docking with AutoDock Vina. Furthermore, we integrated DNA methylation quantitative trait loci (mQTL) data from GoDMC to explore methylation-mediated regulatory mechanisms through mediation MR analysis.ResultsOur transcriptome-wide MR analysis identified 11 high-confidence therapeutic targets in urological cancers: 4 in prostate cancer (BNIP2, KAT5, MMP24, SIK2), 2 in renal cancer (GRB10, GPR17), and 5 in bladder cancer (CELSR1, GPS1, PROC, GSTM1, KLC3). Molecular docking confirmed favorable interactions between these targets and existing drugs. Epigenetic analyses showed DNA methylation-mediated regulation of key targets: PROC (cg09747827) and CELSR1 (cg00784671) in bladder cancer, and SIK2 (cg11344533) in prostate cancer.ConclusionsThis study integrates multi-omics data to identify 11 high-confidence therapeutic targets in urological cancers and is the first to elucidate DNA methylation-mediated regulatory mechanisms for targets like PROC and SIK2. The findings introduce a \"DNA methylation-gene expression\" axis-based strategy for combined targeted-epigenetic therapy, providing crucial evidence for optimizing precision treatment in urological oncology.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"25 ","pages":"15330338261449014"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}