Cancer Medicine最新文献

{"title":"The Role of Noncoding RNA in MGMT-Positive Glioblastoma: A Narrative Review.","authors":"Junfeng Zhao, Jiaxuan Chen, Yingrui Bai, Ying Li, Yiming Han, Chuankun Han, Yintao Li","doi":"10.1002/cam4.72362","DOIUrl":"10.1002/cam4.72362","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive primary malignant tumor of the central nervous system and is characterized by rapid progression, frequent recurrence, and poor survival outcomes. The current standard of care, comprising maximal safe surgical resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ), has improved clinical management; however, the therapeutic benefit remains limited by both intrinsic and acquired resistance to TMZ. O6-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein that removes TMZ-induced O6-methylguanine adducts, is a major determinant of TMZ responsiveness. In particular, methylation of the MGMT promoter is associated with reduced MGMT expression and improved sensitivity to TMZ, although this molecular marker alone does not fully explain interpatient variability in treatment response, which is further modulated by the immunosuppressive tumor microenvironment. Increasing evidence indicates that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), participate in the regulatory network controlling MGMT expression. These ncRNAs may regulate MGMT directly at the posttranscriptional level or indirectly through competing endogenous RNA networks, epigenetic mechanisms, and signaling pathways associated with DNA repair and chemoresistance. Consequently, dysregulated ncRNA expression may contribute to TMZ resistance and GBM progression. Moreover, ncRNAs have potential clinical value as biomarkers for molecular stratification and prognostic assessment, as well as therapeutic targets for restoring TMZ sensitivity. This narrative review summarizes current evidence regarding ncRNA-mediated regulation of MGMT in GBM and discusses the potential implications of targeting these regulatory mechanisms to overcome TMZ resistance.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72362"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Organ-Specific Severe Immune-Related Adverse Events on Long-Term Survival and Treatment Transitions in Metastatic Renal Cell Carcinoma: A 5-Year Multicenter Multistate Analysis.","authors":"Yoshihiko Tasaki, Kazumasa Sato, Shuzo Hamamoto, Yosuke Sugiyama, Hiroaki Ikoma, Kengo Kawase, Hiroko Suzuki, Yusuke Noda, Masayuki Usami, Yohei Tsubouchi, Ryuga Kato, Takuya Sakata, Misato Tomita, Yoshihisa Mimura, Takashi Nagai, Rei Unno, Toshiki Etani, Taku Naiki, Takahiro Yasui, Yoko Furukawa-Hibi","doi":"10.1002/cam4.72410","DOIUrl":"https://doi.org/10.1002/cam4.72410","url":null,"abstract":"<p><strong>Introduction: </strong>Immune-related adverse events (irAEs) frequently occur during combination immune checkpoint inhibition. However, their prognostic impact may vary according to organ involvement and severity. In this study, we exploratorily evaluated whether severe non-endocrine irAEs represent a temporally distinct and prognostically unfavorable clinical phenotype in patients with metastatic renal cell carcinoma (mRCC) treated with ipilimumab plus nivolumab.</p><p><strong>Patients and methods: </strong>We analyzed 63 patients with mRCC treated with ipilimumab plus nivolumab who were followed for at least 5 years. Patients were categorized into non-irAE, non-severe + severe endocrine irAE, and severe non-endocrine irAE groups. Overall survival (OS) was assessed. Multistate modeling was used to evaluate the transitions between treatment, irAE occurrence, and death. Landmark analyses were performed at 8 and 12 weeks to address immortal time bias.</p><p><strong>Results: </strong>The severe non-endocrine irAE group was associated with inferior OS. The multistate analysis revealed a potentially increased risk of direct transition from ipilimumab plus nivolumab to death in the severe non-endocrine irAE group. A significantly higher proportion of patients in the severe non-endocrine irAE group experienced irAEs within 30 days. No significant association was observed in the 8- and 12-week landmark analyses.</p><p><strong>Conclusion: </strong>In this exploratory retrospective study, severe non-endocrine irAEs showed an association with early onset and potentially unfavorable clinical outcomes in patients with mRCC receiving ipilimumab plus nivolumab. Given the limited sample size, these findings should be interpreted cautiously and require confirmation in larger independent cohorts.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72410"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome Analysis Identifies a Myeloid-Like Signature in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Patients With Poor Response to CD19 Chimeric Antigen Receptor T Cell Therapy.","authors":"Shisen Wang, Wenbing Liu, Ying Wang, Yingxi Xu, Haiyan Xing, Kejing Tang, Zheng Tian, Qing Rao, Shaowei Qiu, Hui Wei, Runxia Gu, Min Wang, Jianxiang Wang","doi":"10.1002/cam4.72395","DOIUrl":"https://doi.org/10.1002/cam4.72395","url":null,"abstract":"<p><strong>Background: </strong>Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) patients exhibit heterogeneous responses to CD19 chimeric antigen receptor T-cell (CAR-T) therapy. However, current studies primarily focus on the CAR-T cells or the leukemia blasts, and the patient's intrinsic molecular characteristics before treatment remain poorly understood.</p><p><strong>Methods: </strong>Fifteen R/R B-ALL patients enrolled in a phase II, single-arm clinical trial (NCT04684147) were stratified at a three-month landmark into 8 good responders and 7 poor responders. Clinical characteristics, genetic alterations and pre-treatment bone marrow transcriptomics were compared between groups, and an exploratory gene-expression score was derived.</p><p><strong>Results: </strong>Differential expression and enrichment analyses identified a myeloid-like signature and upregulation of myeloid-related genes in poor responders. Seven myeloid-related genes were examined in independent patient cohorts, in B-ALL cell lines and at single-cell resolution in one patient; three were expressed by the leukemic cells themselves and four predominantly by monocytes and macrophages. A separate, variance-derived seven-gene least absolute shrinkage and selection operator (LASSO) score separated response groups in the discovery cohort (apparent area under the curve, AUC 1.00), with bias-corrected and external estimates of approximately 0.57-0.59 (external cohort AUC 0.592, 95% confidence interval 0.356-0.828).</p><p><strong>Conclusions: </strong>Pre-treatment transcriptomic profiling revealed a myeloid-like signature in R/R B-ALL patients with poor CD19 CAR-T response, warranting further investigation as a candidate correlate of treatment outcome.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72395"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Circulating Metabolites and Skin Cancer: A Bidirectional Two-Sample Mendelian Randomization Study.","authors":"Jiangfan Yu, Hongyan Gong, Zhuotong Zeng, Rong Xiao","doi":"10.1002/cam4.72313","DOIUrl":"https://doi.org/10.1002/cam4.72313","url":null,"abstract":"<p><strong>Background: </strong>Skin cancer is the most common type of cancer worldwide, categorized into melanoma and non-melanoma types. While genetics play a crucial role in the development of skin cancer, recent developments in metabolomics have revealed that circulating metabolites influence genetic risk profiles.</p><p><strong>Methods: </strong>In this study, we utilized a bidirectional two-sample Mendelian Randomization (MR) approach, analyzing metabolite datasets from the Canadian Longitudinal Study of Aging (CLSA) and skin cancer datasets from the UK Biobank. Replication analyses were performed with the 10th round of the FinnGen project. Instrumental variables (IVs) were chosen according to established MR criteria and assessed through the Wald ratio, IVW, MR-Egger, and weighted median methods. Various sensitivity analyses were conducted utilizing Cochrane's Q, Egger's intercept, MR-PRESSO, and leave-one-out (LOO) techniques.</p><p><strong>Results: </strong>After meticulous analysis, we identified causal relationships between circulating metabolites and skin cancer risks. Specifically, levels of 1,2-dilinoleoyl-GPE (18:2/18:2), 1-palmitoyl-2-linoleoyl-gpc (16:0/18:2), 1-stearoyl-2-arachidonoyl-gpc (18:0/20:4), 1-stearoyl-2-linoleoyl-gpc (18:0/18:2), and Docosapentaenoate n3 DPA, the ratio of Arachidonate (20:4n6) to oleate to vaccenate (18:1), and Oleoyl-linoleoyl-glycerol (18:1 to 18:2) to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) were linked to non-melanoma skin cancer, whereas levels of trans-urocanate were causally linked to melanoma of skin, and S-adenosylhomocysteine (SAH) showed a putative association. It should be noted that docosapentaenoate n3 DPA and SAH were each supported by a single SNP and should be interpreted as hypothesis-generating rather than definitive causal evidence. Reverse MR analysis highlighted robust causal relationships with 18 and 10 metabolites and non-melanoma skin cancer and melanoma of skin, respectively.</p><p><strong>Conclusion: </strong>These findings enhance our understanding of skin cancer etiology and risk factors, providing genetic evidence for hypothesis-generating associations that support the development of targeted therapies and aid in the identification of potential biomarkers.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72313"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re: Research Article: Emotional Reactivity and Regulation Relate to Surgical Treatment Decision Making Among Newly Diagnosed Women With Breast Cancer.","authors":"Dorothy Levine, Alvin Rosenfeld, Lisa C Rosenfeld","doi":"10.1002/cam4.72290","DOIUrl":"10.1002/cam4.72290","url":null,"abstract":"","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72290"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Emotional Freedom Techniques on Death Anxiety and Cancer-Related Anxiety in Patients Undergoing Oncological Surgery: A Randomized Controlled Trial.","authors":"Şerafettin Okutan, Gürkan Kapikiran, Remziye Cici, Seher Çevik Aktura","doi":"10.1002/cam4.72307","DOIUrl":"10.1002/cam4.72307","url":null,"abstract":"<p><p>This study was conducted to investigate the effect of emotional freedom techniques (EFT) on death anxiety in patients experiencing postsurgery cancer-related anxiety. A total of 120 oncological surgical patients were randomly allocated to either the intervention group (n = 60) or the control group (n = 60). Data were collected from February 2025 to September 2025 as a randomized controlled trial. While EFT (once a day, for 3 days) was applied to the patients in the intervention group in addition to the clinical procedure, the control group only followed the clinical procedure without any intervention. Following EFT, participants in the intervention group showed statistically significant reductions in both cancer-related anxiety and death anxiety scores (p < 0.001). The decrease in subjective distress scores in the intervention group after EFT was found to be significant (p < 0.001). When the intervention and control groups were compared based on their final test scores, the intervention group had lower levels of cancer-related anxiety, death anxiety, and subjective distress (p < 0.05). Clinical EFT application demonstrated immediate postintervention efficacy in reducing death anxiety, cancer-related anxiety, and subjective distress. However, due to the absence of a long-term follow-up period, these findings reflect acute psychological stabilization.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72307"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated scRNA-Seq and Spatial Transcriptomics Reveal CHPF and GPC1 as Markers of Cancer-Associated Fibroblast-Dominant Domains in Colorectal Cancer.","authors":"Yuan-Jie Liu, Qian-Wen Ye, Hui Zhang, Ning Yang, Yang Li, Jie-Pin Li","doi":"10.1002/cam4.72369","DOIUrl":"10.1002/cam4.72369","url":null,"abstract":"<p><p>Spatial heterogeneity in the colorectal cancer (CRC) tumor microenvironment (TME) is closely related to stromal organization and may influence treatment-related features. In this study, we integrated single-cell RNA sequencing and spatial transcriptomic data from CRC tissues to examine cancer-associated fibroblast (CAF)-dominant spatial domains. GPC1 and CHPF were enriched in stromal regions and showed higher expression in CRC tissues than in normal tissues. In the analyzed cohorts, higher GPC1 and CHPF expression was associated with advanced clinicopathological features and poorer survival outcomes in univariate analyses. Single-cell analyses showed that GPC1 and CHPF were mainly expressed in fibroblasts and were enriched in an ADAM12-associated fibroblast subset with myofibroblast-like features, extracellular matrix-related genes, and hypoxia/glycolysis-related signatures. Cell-cell communication analysis suggested that this fibroblast subset was linked to higher inferred WNT signaling. Drug-response and immunotherapy-related analyses further showed that GPC1 and CHPF expression was associated with transcriptomic patterns related to treatment response. In mucinous adenocarcinoma (MA), the ADAM12-associated fibroblast program showed stronger inferred MIF-related signaling and was associated with macrophage M2-like features. Spatial mapping and multiplex immunofluorescence supported partial colocalization of GPC1, CHPF, and ADAM12 in CAF-rich stromal regions. In CAFs, GPC1 or CHPF knockdown reduced ADAM12, CAF activation markers, and WNT/MIF-related proteins, while ADAM12 knockdown weakened macrophage M2-like marker expression in a co-culture model. These findings suggest that GPC1 and CHPF mark an ADAM12-associated CAF program linked to stromal remodeling and immune-related features in CRC, especially in MA, but further studies are needed to define its functional role.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72369"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Overall Survival With Abiraterone Acetate and Enzalutamide in Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer From the Flatiron Electronic Health Records Database.","authors":"Daniel J George, Jasmina I Ivanova, Maëlys Touya, Betty Thompson, Jonathan Assayag, Benjamin Li, Nikolaos Kountouris, Gordon Siu, Stephen J Freedland","doi":"10.1002/cam4.72356","DOIUrl":"10.1002/cam4.72356","url":null,"abstract":"<p><strong>Background: </strong>Patients with chemotherapy- and androgen receptor pathway inhibitor (ARPI)-naïve metastatic castration-resistant prostate cancer (mCRPC) have generally shown worse overall survival (OS) with abiraterone versus enzalutamide in claims database studies. Given limitations of claims data, analysis using detailed electronic health records (EHRs) is needed to confirm this finding.</p><p><strong>Methods: </strong>This EHR-based analysis (2014-2023) of the Flatiron Health database included patients with chemotherapy- and ARPI-naïve mCRPC who initiated first-line ARPI (abiraterone or enzalutamide). OS, treatment duration, and time to subsequent therapy were assessed. A subgroup analysis evaluated patients who received first-line ARPI only with no subsequent treatments. Kaplan-Meier method and Cox proportional hazards models evaluated time-to-event outcomes. Stabilized inverse probability treatment weighting (sIPTW) adjusted for baseline differences.</p><p><strong>Results: </strong>Among 2731 patients, 1316 received first-line abiraterone and 1415 enzalutamide (median follow-up: 21.8 and 23.2 months, respectively). sIPTW-adjusted median OS (24.6 vs. 25.8 months; hazard ratio [HR] 1.13; 95% confidence interval [CI], 1.03-1.23), treatment duration (7.9 vs. 9.5 months; HR 1.21; 95% CI, 1.11-1.31), and time to subsequent therapy (14.7 vs. 17.9 months; HR 1.20; 95% CI, 1.08-1.32) were shorter with abiraterone versus enzalutamide. Among the 40% with no subsequent treatment (n = 1102), sIPTW-adjusted median OS (14.0 vs. 17.7 months; HR 1.32; 95% CI, 1.14-1.53), and treatment duration (7.5 vs. 10.6 months; HR 1.30; 95% CI, 1.12-1.50) were also shorter with abiraterone versus enzalutamide.</p><p><strong>Conclusions: </strong>Using more detailed data abstraction, these results confirm prior claims-based analyses showing that despite early use of subsequent therapy, first-line abiraterone is associated with shorter OS versus enzalutamide in ARPI- and chemotherapy-naïve mCRPC.</p><p><strong>Trial registration: </strong>Clinical Trial ID: NCT05968599.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72356"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infection Profiles Under Venetoclax-Based Therapy in Newly Diagnosed Acute Myeloid Leukemia: A Real-World Study.","authors":"Guilin Ren, Guangyu Zhou, Hao Zhou, Xi Dou, Lin Liu, Jianbin Chen, Xiaoqiong Tang, Hongbin Zhang, Xin Wang, Xiaohua Luo, Li Wang","doi":"10.1002/cam4.72087","DOIUrl":"10.1002/cam4.72087","url":null,"abstract":"<p><p>Venetoclax (VEN)-based regimens improve remission in acute myeloid leukemia (AML), but infectious toxicity remains a concern. We compared infection profiles under VEN-based versus conventional therapy in newly diagnosed, non-M3 AML at a single tertiary center (2015-2024; n = 358; VEN = 156; non-VEN = 202). After 1:1 propensity-score matching on nine baseline covariates (115 per group), we assessed infection rates and event density (events per 1000 person-days) by site and pathogen, time to first infection (120-day cumulative incidence), and landmark associations between early infections and progression-free survival (PFS). Baseline predictors of microbiologically documented infection (MDI) were modeled in the pre-matching cohort. VEN was associated with higher febrile-neutropenia (FN) event density (IRR, 1.77; 95% CI, 1.33-2.36; p < 0.001; 16.40 vs. 9.27 per 1000 person-days). Site-level patterns diverged: upper-respiratory and lung infections showed lower first-event incidence with VEN, whereas skin/soft-tissue and perianal sites showed higher event density without higher patient-level incidence. By pathogen, bacterial and fungal first events were fewer with VEN while event densities were comparable; viral infections occurred earlier and accrued higher cumulative incidence. Cumulatively, the first infection was lower with VEN at days 30, 60, and 90 but converged by day 120. In the pre-matching cohort, higher HCT-CI (1-2/≥ 3 vs. 0) and higher DBIL independently predicted MDI, while female sex predicted lower risk. MDIs within 90 days-bacterial/fungal-driven-were associated with inferior PFS at 100 and 365 days, whereas early viral infections showed no association.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72087"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Therapy for Metastatic Castration-Resistant Prostate Cancer Using the JC Polyomavirus (JCPyV) Virus-Like Particles as a Gene Delivery Vector.","authors":"Chih-Chieh Chou, Chih-En Tseng, Yu-Shih Lin, Meilin Wang, Pei-Lain Chen, Deching Chang, Cheng-Huang Shen, Chiung-Yao Fang","doi":"10.1002/cam4.72365","DOIUrl":"https://doi.org/10.1002/cam4.72365","url":null,"abstract":"<p><strong>Background: </strong>Systemic metastasis remains the leading cause of mortality in patients with advanced prostate cancer, particularly in castration-resistant prostate cancer (CRPC), for which effective systemic therapeutic options are limited. Gene therapy is a potential strategy for achieving selective tumor targeting and systemic disease control in metastatic settings. This study aimed to establish a systemic metastasis animal model for CRPC and evaluate the therapeutic efficacy of JC polyomavirus (JCPyV) virus-like particle (VLPs)-based gene therapy against metastatic disease.</p><p><strong>Methods: </strong>A near-infrared fluorescent protein (iRFP)-expressing CRPC cell line was used to establish a systemic metastasis model by tail-vein injection in mice. The therapeutic efficacy of JCPyV VLPs carrying a prostate-specific antigen (PSA) promoter-driven suicide gene (PSAtk-VLPs), administered in combination with ganciclovir (GCV), was evaluated longitudinally by fluorescence molecular tomography (FMT), with enzalutamide/leuprorelin acetate (ENZ/LEU) included as a clinical treatment comparator.</p><p><strong>Results: </strong>CRPC metastases in the lungs, liver, spleen, kidneys, and bones were detected by FMT in real time. Control mice exhibited exponential CRPC growth, whereas ENZ/LEU treatment delayed CRPC progression. PSAtk-VLPs/GCV significantly inhibited the growth of metastatic CRPC. However, no significant differences in survival were observed among the MOCK, ENZ/LEU, and PSAtk-VLP/GCV groups (log-rank test, p = 0.7351).</p><p><strong>Conclusion: </strong>These findings support that JCPyV-derived virus-like particles constitute a promising therapeutic approach for metastatic CRPC, enabling systemic delivery of suicide gene therapy with selective inhibition of tumor growth and translational relevance.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72365"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}