British Journal of Cancer最新文献_第3页

An ABCC1-based risk model is effective in the diagnosis of synchronous peritoneal metastasis in advanced colorectal cancer. 基于abcc1的风险模型可有效诊断晚期结直肠癌腹膜同步转移。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-09-26 DOI: 10.1038/s41416-025-03203-1

Wenqing Xie, Qianxin Luo, Zhimei Ou, Wanjun Liu, Minghan Huang, Qian Wang, Ping Lan, Daici Chen

{"title":"An ABCC1-based risk model is effective in the diagnosis of synchronous peritoneal metastasis in advanced colorectal cancer.","authors":"Wenqing Xie, Qianxin Luo, Zhimei Ou, Wanjun Liu, Minghan Huang, Qian Wang, Ping Lan, Daici Chen","doi":"10.1038/s41416-025-03203-1","DOIUrl":"https://doi.org/10.1038/s41416-025-03203-1","url":null,"abstract":"Background: The presence of peritoneal metastasis (PM) in colorectal cancer (CRC) patients indicates an advanced CRC stage. Prompt diagnosis and early PM detection are difficult, and the underlying mechanisms are unclear, resulting in limited treatment options and unsatisfactory therapeutic effects. We aimed to identify applicable biomarkers for accurately diagnosing synchronous PM in CRC patients.Methods: Differentially expressed genes between synchronous and non-synchronous PM groups were identified via label-free proteomic analysis of primary tumors from 31 CRC patients. Quantitative real-time PCR, multiplex and conventional immunohistochemistry were used to validate gene expression. We attempted to construct a logistic regression risk model for the diagnosis of PM, which was tested in a training cohort and validated in an independent cohort.Results: Utilizing the results from multi-omics, we established an ABCC1-based risk model. In CRC patients with imaging-negative diagnoses, the model identified patients with metastases including PM (AUC = 0.892, 95% CI: 0.840-0.944) or those with PM only (AUC = 0.859, 95% CI: 0.794-0.924); these results were validated in an independent cohort of patients with metastases including PM (AUC = 0.831, 95% CI: 0.729-0.933) or PM only (AUC = 0.819, 95% CI: 0.702-0.936). In CRC patients with CEA-negative, this model more effectively distinguishes those with exclusive peritoneal involvement, with consistent results across both training (AUC = 0.913, 95% CI: 0.854-0.972) and validation (AUC = 0.869, 95% CI: 0.795-0.943) cohorts. Additionally, in CRC patients with PM, low ABCC1 may serve as a predictive marker for chemotherapy efficacy.Conclusions: The ABCC1-based risk model effectively predicts PM in CRC, complementing traditional diagnostics. ABCC1 may serve as a predictive marker for chemotherapy efficacy in PM.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gemcitabine-induced neutrophil extracellular traps via interleukin-8-CXCR1/2 pathway promote chemoresistance in pancreatic cancer. 吉西他滨通过白细胞介素-8- cxcr1 /2途径诱导的中性粒细胞胞外陷阱促进胰腺癌的化疗耐药。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-09-25 DOI: 10.1038/s41416-025-03192-1

Shohei Nogi, Shunsuke Kagawa, Atsuki Taniguchi, Tomohiko Yagi, Nobuhiko Kanaya, Yoshihiko Kakiuchi, Kazuya Yasui, Tomokazu Fuji, Yoshiyasu Kono, Satoru Kikuchi, Kosei Takagi, Shinji Kuroda, Fuminori Teraishi, Hiroshi Tazawa, Toshiyoshi Fujiwara

{"title":"Gemcitabine-induced neutrophil extracellular traps via interleukin-8-CXCR1/2 pathway promote chemoresistance in pancreatic cancer.","authors":"Shohei Nogi, Shunsuke Kagawa, Atsuki Taniguchi, Tomohiko Yagi, Nobuhiko Kanaya, Yoshihiko Kakiuchi, Kazuya Yasui, Tomokazu Fuji, Yoshiyasu Kono, Satoru Kikuchi, Kosei Takagi, Shinji Kuroda, Fuminori Teraishi, Hiroshi Tazawa, Toshiyoshi Fujiwara","doi":"10.1038/s41416-025-03192-1","DOIUrl":"https://doi.org/10.1038/s41416-025-03192-1","url":null,"abstract":"Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, and chemoresistance poses a significant challenge in its treatment. Neutrophil extracellular traps (NETs) have emerged as key players in the tumour microenvironment, but their role in chemoresistance remains unclear.Methods: We investigated the involvement of NETs in PDAC chemoresistance using patient tumour samples, in vitro assays with gemcitabine (GEM)-treated PDAC cells, and in vivo mouse models. We evaluated cytokine production, NET formation and tumour response to GEM, with or without the CXCR1/2 inhibitor navarixin.Results: NETs are significantly accumulated in the tumours of PDAC patients exhibiting poor response to chemotherapy. GEM-treated PDAC cells secrete pro-inflammatory cytokines such as interleukin-8 (IL-8). IL-8 promote the formation of chemotherapy-induced NETs (chemoNETosis) through activation of CXCR 1/2 on neutrophils. Importantly, treatment with navarixin significantly suppressed chemoNETosis, restored sensitivity to GEM, and significantly reduced tumour growth in vivo.Conclusions: Our findings reveal that NETs contribute to chemoresistance in PDAC and that IL-8-mediated chemoNETosis plays a pivotal role in this process. Inhibition of CXCR1/2-mediated NET formation enhances the efficacy of GEM. This approach may represent a promising therapeutic strategy for overcoming chemoresistance in PDAC. These results support further clinical investigation of anti-NETs therapies.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction Note: Toll-like receptor 9 agonist IMO cooperates with everolimus in renal cell carcinoma by interfering with tumour growth and angiogenesis. 注：toll样受体9激动剂IMO通过干扰肿瘤生长和血管生成与依维莫司合作治疗肾细胞癌。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-09-25 DOI: 10.1038/s41416-025-03214-y

V Damiano, R Rosa, L Formisano, L Nappi, T Gelardi, R Marciano, I Cozzolino, G Troncone, S Agrawal, B M Veneziani, S De Placido, R Bianco, G Tortora

引用次数: 0

Ethnic disparities in opioid prescribing for cancer pain and associated emergency department visits and hospital admissions in the last three months of life: a retrospective cohort study. 癌症疼痛阿片类药物处方的种族差异以及生命最后三个月的相关急诊就诊和住院：一项回顾性队列研究

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-09-25 DOI: 10.1038/s41416-025-03200-4

Emeka Chukwusa, Sophie Law-Clucas, Martin Gulliford, Sabrina Bajwah, Stephen Barclay, Rashmi Kumar, Gemma Clarke, Tanya Siriwimala, Jonathan Koffman

{"title":"Ethnic disparities in opioid prescribing for cancer pain and associated emergency department visits and hospital admissions in the last three months of life: a retrospective cohort study.","authors":"Emeka Chukwusa, Sophie Law-Clucas, Martin Gulliford, Sabrina Bajwah, Stephen Barclay, Rashmi Kumar, Gemma Clarke, Tanya Siriwimala, Jonathan Koffman","doi":"10.1038/s41416-025-03200-4","DOIUrl":"https://doi.org/10.1038/s41416-025-03200-4","url":null,"abstract":"Background: Ethnic inequalities in pain management at the end of life remain underexplored in the UK. We examined associations between patient ethnicity, opioid prescribing, and related healthcare use among cancer decedents.Methods: Retrospective cohort study including 232,329 adults (≥18 years) diagnosed with cancer between 2011 and 2021. Primary care records from the Clinical Practice Research Datalink Aurum were linked to hospital and mortality data. Person-time rates of opioid prescriptions, emergency department (ED) visits, and hospital admissions in the last three months of life were estimated. Poisson regression with Generalised Estimating Equations generated adjusted rate ratios (aRRs) and 95% confidence intervals (CIs), controlling for relevant covariates.Results: Of 3,987,635 opioid prescriptions, 620,232 (16%) occurred in the final three months. Prescription rates were highest among White patients (969.97-894.43/1000 person-months). Compared with White patients, prescribing was significantly lower among Black (aRR 0.91, 95% CI 0.87-0.95), South Asian (aRR0.93, CI0.89-0.97), Mixed (aRR 0.85, CI 0.79-0.92) and Other ethnic groups (aRR 0.90, CI 0.85-0.96). Patients from minority ethnic backgrounds, particularly Black and South Asian, more often experienced ≥2 ED visits and ≥2 hospital admissions.Conclusion: Minority ethnic patients with cancer receive fewer opioids and experience higher acute care use near the end of life. Tackling system-level inequities is critical to achieving pain management.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transforming histologic assessment: artificial intelligence in cancer diagnosis and personalized treatment. 改变组织学评估：人工智能在癌症诊断和个性化治疗中的应用。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-09-24 DOI: 10.1038/s41416-025-03206-y

Manabu Takamatsu

{"title":"Transforming histologic assessment: artificial intelligence in cancer diagnosis and personalized treatment.","authors":"Manabu Takamatsu","doi":"10.1038/s41416-025-03206-y","DOIUrl":"https://doi.org/10.1038/s41416-025-03206-y","url":null,"abstract":"Artificial intelligence (AI) is transforming histologic assessment, evolving from a diagnostic adjunct to an integral component of clinical decision-making. Over the past decade, AI applications have significantly advanced histopathology, facilitating tasks from tissue classification to predicting cancer prognosis, gene alterations, and therapy responses. These developments are supported by the availability of high-quality whole-slide images (WSIs) and publicly accessible databases like The Cancer Genome Atlas (TCGA), which integrate histologic, genomic, and clinical data. Deep learning techniques replicate and enhance pathologists' decisions, addressing challenges such as inter-observer variability and diagnostic reproducibility. Moreover, AI enables robust predictions of patient prognosis, actionable gene statuses, and therapy responses, offering rapid, cost-effective alternatives to conventional methods. Innovations such as histomorphologic phenotype clusters and spatial transcriptomics have further refined cancer stratification and treatment personalization. In addition, multimodal approaches integrating histologic images with clinical and molecular data have achieved superior predictive accuracy and explainability. Nevertheless, challenges remain in verifying AI predictions, particularly for prognostic applications and ensuring accessibility in resource-limited settings. Addressing these challenges will require standardized datasets, ethical frameworks, and scalable infrastructure. While AI is revolutionizing histologic assessment for cancer diagnosis and treatment, optimizing digital infrastructure and long-term strategies is essential for its widespread adoption in clinical practice.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vaginal germ cell tumors: results from the international retrospective VAGIPED study. 阴道生殖细胞肿瘤：国际回顾性VAGIPED研究的结果。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-09-24 DOI: 10.1038/s41416-025-03201-3

Cécile Faure-Conter, Luiz Fernando Lopes, Yijin Gao, Gabriele Calaminus, Monica Terenziani, Maria Debora De Pasquale, Agnes Vojcek, Orjana Velikonja, Joanna Stefanowicz, Shayi Jiang, Xiaojun Yuan, Yali Han, Ricardo López-Almaraz, Anthony Penn, Claire Stokes, Michelle Nuno, Lindsay Frazier, Deborah F Billmire, Brice Fresneau, Claire Cropet

{"title":"Vaginal germ cell tumors: results from the international retrospective VAGIPED study.","authors":"Cécile Faure-Conter, Luiz Fernando Lopes, Yijin Gao, Gabriele Calaminus, Monica Terenziani, Maria Debora De Pasquale, Agnes Vojcek, Orjana Velikonja, Joanna Stefanowicz, Shayi Jiang, Xiaojun Yuan, Yali Han, Ricardo López-Almaraz, Anthony Penn, Claire Stokes, Michelle Nuno, Lindsay Frazier, Deborah F Billmire, Brice Fresneau, Claire Cropet","doi":"10.1038/s41416-025-03201-3","DOIUrl":"https://doi.org/10.1038/s41416-025-03201-3","url":null,"abstract":"Background: Vaginal malignant germ cell tumors (MGCTs), predominantly yolk sac tumors, are extremely rare, with no established consensus on optimal management. This study evaluated whether post-chemotherapy surgery is necessary for vaginal MGCTs.Methods: A retrospective analysis was conducted on patients diagnosed with vaginal MGCTs from 1996 to 2023. Progression-free survival (PFS), overall survival (OS), the impact of surgical intervention, and the presence of post-chemotherapy residual mass (RM) were assessed.Results: Seventy-five patients (median age:11 months) were included. Six underwent initial tumor resection, and all received platinum-based chemotherapy. RM was detected post-chemotherapy in 57% of evaluable cases (40/70), with vaginoscopy outperforming standard imaging in detection (p < 0.001). The 5-year PFS and OS rates were 83% (95%CI: 71-90) and 94% (95%CI: 84-98), respectively. Neither RM (p = 0.64) nor delayed surgical intervention (5-year PFS: 77% (95%CI: 54-90) without surgery versus 85% (95%CI: 70-92) with surgery; log-rank test p = 0.72) significantly impacted PFS.Discussion: Neoadjuvant platinum-based chemotherapy yields excellent survival outcomes in vaginal MGCTs. Vaginoscopy appears more sensitive than standard imaging for RM detection and is recommended for post-chemotherapy evaluation. In the absence of RM on vaginoscopy and with negative tumor markers, systematic post-chemotherapy surgery may be unnecessary. A global consensual framework for managing is proposed.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Factors that influence the uptake of precision-guided treatment recommendations in paediatric cancer: a systematic review. 影响儿童癌症采用精确指导治疗建议的因素：系统综述

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-09-24 DOI: 10.1038/s41416-025-03171-6

Xian Zou, Tarini Srivastava, Kate Hetherington, Alice Yu, Glenn M Marshall, Marion K Mateos

{"title":"Factors that influence the uptake of precision-guided treatment recommendations in paediatric cancer: a systematic review.","authors":"Xian Zou, Tarini Srivastava, Kate Hetherington, Alice Yu, Glenn M Marshall, Marion K Mateos","doi":"10.1038/s41416-025-03171-6","DOIUrl":"https://doi.org/10.1038/s41416-025-03171-6","url":null,"abstract":"Despite potential benefits, the clinical uptake of precision-guided treatment (PGT) in paediatric oncology remains low. This systematic review aimed to identify factors affecting the adoption of PGT recommendations for children with cancer. Five databases (EMBASE, CINAHL, PubMed, PsycINFO, Scopus) were systematically searched. Qualitative and quantitative studies involving patients aged 0-21 years were included. Two reviewers conducted screening and data extraction. Seventeen studies, all from developed countries, met the criteria: 10 prospective, 4 retrospective, and 3 cross-sectional, involving 3976 patients, 227 healthcare professionals, 189 parents, and 532 community members. Most studies were quantitative, collating factors from clinical records; two qualitative studies used interviews to explore clinician and parent perspectives. Three key domains of factors were identified: (i) decision maker-related characteristics; (ii) decision-specific criteria; and (iii) contextual factors. Common factors included limited drug/clinical trial access, ongoing alternative treatments, high costs, and patient or family preferences. These interlinked factors may affect uptake individually and collectively. To our knowledge, this is the first review to map factors influencing the implementation of PGT in paediatric cancer. Further research is needed to clarify the relative importance of these factors and to better understand oncologists' perspectives when making recommendations in partnership with patients and families. REGISTRATION: PROSPERO database (CRD42023410199).","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adverse events of postoperative adjuvant chemotherapy predict survival outcomes in locally advanced colorectal cancer: a pooled analysis of Japanese clinical trials. 术后辅助化疗不良事件预测局部晚期结直肠癌患者的生存结局：日本临床试验的汇总分析

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-09-22 DOI: 10.1038/s41416-025-03199-8

Hidetaka Kawamura, Michitaka Honda, Yujiro Nakayama, Koji Oba, Masaru Muto, Toru Aoyama, Mitsuro Kanda, Hiromichi Maeda, Shuhei Mayanagi, Kosuke Kashiwabara, Kenji Tanaka, Junichi Sakamoto, Hisakazu Yamagishi, Takaki Yoshikawa

{"title":"Adverse events of postoperative adjuvant chemotherapy predict survival outcomes in locally advanced colorectal cancer: a pooled analysis of Japanese clinical trials.","authors":"Hidetaka Kawamura, Michitaka Honda, Yujiro Nakayama, Koji Oba, Masaru Muto, Toru Aoyama, Mitsuro Kanda, Hiromichi Maeda, Shuhei Mayanagi, Kosuke Kashiwabara, Kenji Tanaka, Junichi Sakamoto, Hisakazu Yamagishi, Takaki Yoshikawa","doi":"10.1038/s41416-025-03199-8","DOIUrl":"https://doi.org/10.1038/s41416-025-03199-8","url":null,"abstract":"Background: Adverse events during postoperative adjuvant chemotherapy may reflect prognosis in resectable advanced colorectal cancer. This study assessed the association between these events and survival in advanced colorectal cancer patients.Methods: We analysed patient data from four Japanese randomised controlled trials on adjuvant chemotherapy for stage II or III colorectal cancer. Adverse events were defined as the maximum grade within 6 months. The primary outcome was overall survival, analysed using a multivariate-adjusted Cox proportional hazard model.Results: A total of 4,046 patients with advanced colorectal cancer undergoing adjuvant chemotherapy were included. Maximum adverse event grades were: 739 (18%) grade 0, 960 (24%) grade 1, 1511 (37%) grade 2, 779 (19%) grade 3 and 57 (1.4%) grade 4. Compared to grade 0, hazard ratios for overall survival were 0.77 (95% CI, 0.61-0.98) for grade 1, 0.70 (95% CI, 0.56-0.87) for grade 2, 0.69 (95% CI, 0.53-0.91) for grade 3 and 1.12 (95% CI, 0.62-2.04) for grade 4.Conclusions: The severity of adverse events during adjuvant chemotherapy correlated with survival outcomes in advanced colorectal cancer. Mild to moderate events were linked to improved prognosis, while absence suggested poorer outcomes, indicating a need for alternative treatments.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

UDP-glucose ceramide glucosyltransferase promotes radioresistance via membrane reorganization to maintain redox balance in glioblastoma. udp -葡萄糖神经酰胺葡萄糖基转移酶通过膜重组促进辐射抗性，以维持胶质母细胞瘤的氧化还原平衡。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-09-22 DOI: 10.1038/s41416-025-03191-2

Haksoo Lee, Dahye Kim, Byeongsoo Kim, DongJoo Joung, Jaewan Jeon, Tae-Oh Kim, HyeSook Youn, BuHyun Youn

{"title":"UDP-glucose ceramide glucosyltransferase promotes radioresistance via membrane reorganization to maintain redox balance in glioblastoma.","authors":"Haksoo Lee, Dahye Kim, Byeongsoo Kim, DongJoo Joung, Jaewan Jeon, Tae-Oh Kim, HyeSook Youn, BuHyun Youn","doi":"10.1038/s41416-025-03191-2","DOIUrl":"https://doi.org/10.1038/s41416-025-03191-2","url":null,"abstract":"Background: Glioblastoma (GBM) is an aggressive brain tumor characterized by a poor prognosis and resistance to radiotherapy. Although multiple mechanisms of radioresistance have been proposed, the contribution of membrane-driven metabolic adaptations to radioresistance remains poorly understood.Methods: The role of UDP-glucose ceramide glucosyltransferase (UGCG) was investigated using radioresistant GBM cell lines and in vivo xenograft models. After inhibiting UGCG function through genetic or pharmacological (miglustat) approaches, we assessed the effects on lipid raft integrity, localization of the ASCT2 transporter, glutamine uptake, oxidative stress, and radiosensitivity.Results: UGCG was upregulated in radioresistant GBM cells and promoted lipid raft stabilization. This facilitated the membrane recruitment of the glutamine transporter ASCT2 (SLC1A5), thereby sustaining redox homeostasis under radiation stress. Genetic or pharmacological inhibition of UGCG disrupted lipid raft integrity, impaired ASCT2 localization, reduced glutamine uptake, and increased oxidative stress, leading to enhanced radiosensitivity. In GBM xenograft models, UGCG inhibition combined with radiotherapy significantly suppressed tumor growth and extended survival.Conclusions: These findings reveal a previously underexplored, membrane-centric mechanism of radioresistance in which UGCG orchestrates lipid raft remodeling to facilitate glutamine-dependent redox balance. This highlights UGCG as a potential therapeutic target to enhance the efficacy of radiotherapy in GBM.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ENO1 promotes cancer metastasis via stimulating metabolism reprogramming in osteosarcoma. ENO1通过刺激骨肉瘤的代谢重编程促进肿瘤转移。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-09-22 DOI: 10.1038/s41416-025-03182-3

Peng Huang, Shiwei He, Zhi Qi, Yaxier Nijiati, Junfeng Wang, Zichen Lin, Yangyang Ma, Rui Dong, Gong Chen, Bo Ning

{"title":"ENO1 promotes cancer metastasis via stimulating metabolism reprogramming in osteosarcoma.","authors":"Peng Huang, Shiwei He, Zhi Qi, Yaxier Nijiati, Junfeng Wang, Zichen Lin, Yangyang Ma, Rui Dong, Gong Chen, Bo Ning","doi":"10.1038/s41416-025-03182-3","DOIUrl":"https://doi.org/10.1038/s41416-025-03182-3","url":null,"abstract":"Background: This study aims to unravel the underlying mechanisms of osteosarcoma (OS) metastasis by single-cell RNA-sequencing.Methods: Ten pediatrics OS samples were analyzed using scRNA-seq and divided into three groups: primary tumor without lung metastasis (Pri_non_MT), primary tumor with lung metastasis (Pri_MT), and lung metastasis site (MT). Candidate genes associated with metastasis were identified by bioinformatics analysis and was confirmed at mRNA and protein levels in OS tissues. The function of candidate gene was identified in vitro and in vivo. Bulk RNA sequencing was used to explore downstream mechanism after candidate gene silenced.Results: A total of 17 cell clusters were identified. ENO1 was selected as the candidate gene and was significantly expressed in Pri_MT and MT groups. In OS tissues, ENO1 significantly overexpressed in patients with lung metastasis compared to those without. Knocking down ENO1 resulted in a marked decrease in migration and invasion in vitro and a reduction in lung metastasis in vivo. Additionally, ENO1 suppression resulted in shifting the primary ATP production pathway from glycolysis to oxidative phosphorylation.Conclusions: Our findings highlight ENO1 as a key regulator of glycolysis and metastasis in osteosarcoma, offering a novel therapeutic target for OS treatment.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0