British Journal of Cancer最新文献

{"title":"Mapping B7-H3 in the tumour microenvironment: a systematic review of stromal, vascular and immune expression.","authors":"Laura Privitera, Piero Alberti, Simone Oliver Senica, Jonathan J Neville, Judith Wienke, John Anderson, Stefano Giuliani","doi":"10.1038/s41416-026-03573-0","DOIUrl":"https://doi.org/10.1038/s41416-026-03573-0","url":null,"abstract":"<p><p>B7 homologue 3 (B7-H3) is a promising therapeutic target in oncology. While its expression on tumour cells is well established, its distribution and role within the tumour microenvironment (TME) remain less clearly defined. This review systematically evaluates B7-H3 protein expression across human TME compartments and explores reported associations with tumour progression and clinical outcomes. A comprehensive literature search was conducted up to June 2025, identifying studies that assessed and quantified B7-H3 expression in the TME of solid human tumours. Thirty-one studies met the inclusion criteria. B7-H3 expression was frequently reported in tumour-associated vasculature, where higher levels have been reported to associate with aggressive histopathological features and reduced survival. Stromal expression, predominantly in cancer-associated fibroblasts, was identified in over half of the tumour types studied and was associated with immune evasion and stromal remodelling gene signatures, although findings varied across studies. Within the immune compartment, B7-H3 was most abundantly expressed in myeloid-derived suppressor cells, macrophages, and dendritic cells, and has been reported to associate to immunosuppressive phenotypes, advanced disease stage and poorer clinical outcomes. These findings identify tumour vasculature and myeloid-derived cells as B7-H3-positive compartments within the TME, although their clinical and therapeutic relevance requires further validation. PROSPERO registration number: CRD420251129792.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788267","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}

{"title":"Risk of urologic cancers in patients with hospital-diagnosed recurrent cystitis: a nationwide population-based study.","authors":"Kasper Kjersgaard Mortensen, Kirstine Kobberøe Søgaard, Dóra Körmendiné Farkas, Eyal Oren, Mette Nørgaard, Henrik Toft Sørensen","doi":"10.1038/s41416-026-03591-y","DOIUrl":"https://doi.org/10.1038/s41416-026-03591-y","url":null,"abstract":"<p><strong>Background: </strong>Recurrent infections in the urinary tract may promote urologic cancer through chronic inflammation. However, evidence linking infections and the subsequent risk of urologic cancer has been conflicting, and long-term risk remains uncertain.</p><p><strong>Methods: </strong>In this population-based descriptive cohort study, we included all Danish adults with a first-time hospital discharge diagnosis of recurrent cystitis during 2006-2022 in the Danish National Patient Registry, excluding patients with prior cancer. Urologic cancer diagnoses were ascertained through the Danish Cancer Registry. We calculated cumulative incidences and standardised incidence ratios (SIRs) using incidence rates from the general population.</p><p><strong>Results: </strong>Among 42,377 patients (68% women, median age 62 years), 1047 were diagnosed with urologic cancer (median follow-up 5.7 years). The 1-year risk of any urologic cancer was 1.2% (95% confidence interval [CI], 1.1-1.3%). The corresponding 1-year SIR was 4.99 (95% CI, 4.56-5.44). Beyond 2 years of follow-up, the SIR remained elevated among women only at 1.47 (95% CI, 1.20-1.78).</p><p><strong>Conclusions: </strong>The elevated short-term risk suggests that recurrent cystitis is a clinical marker of urologic cancer. Yet, with low absolute risks, our results do not suggest additional diagnostic cancer work-up in these patients. In women, long-term risks for urologic cancer remained elevated.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788401","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}

{"title":"Immune and stromal tumour biology associated with neoadjuvant radiotherapy response in locally advanced rectal cancer.","authors":"Lily V S Hillson, Ashley K McCulloch, Ross K McMahon, Phimmada Hatthakarnkul, Aula Ammar, Timothy S Maughan, Enric Domingo, Sudhir B Malla, Raheleh Amirkhah, James H Park, Joanne Edwards, Philip D Dunne, Sean M O'Cathail, Campbell S Roxburgh","doi":"10.1038/s41416-026-03575-y","DOIUrl":"https://doi.org/10.1038/s41416-026-03575-y","url":null,"abstract":"<p><strong>Background: </strong>Response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer (LARC) is heterogeneous. The Neoadjuvant Rectal (NAR) score quantifies treatment response via tumour downstaging and nodal status and correlates with survival outcomes. This work set out to explore whether low NAR and high NAR tumours represent biologically distinct groups pre-treatment.</p><p><strong>Methods: </strong>Transcriptome microarrays quantified RNA expression within pre-treatment biopsies from LARC patients in GSE87211 and S:CORT consortium Grampian datasets. A validation cohort from the Beatson West of Scotland Cancer Centre was analysed using multiplex immunofluorescence and H&E-derived tumour-stromal ratios.</p><p><strong>Results: </strong>Seventeen MSigDB Hallmarks were enriched in high NAR tumours; 'Epithelial-Mesenchymal Transition' was notably enriched (padj < 0.001). Immune-related signatures were enriched in low NAR tumours (p < 0.25). Both cohorts showed higher Microenvironment Cell Population counter 'Cytotoxic Lymphocytes' in low NAR (p < 0.05) and more stromal cells ('Endothelial Cells', 'Fibroblasts'; p < 0.05) in high NAR tumours. CD8 densities confirmed higher immune infiltration in low NAR tumours.</p><p><strong>Discussion: </strong>Pre-treatment biopsies show consistent microenvironmental differences between high and low NAR tumours. While immune and stromal features are associated with response, the observed differences are insufficient to serve as standalone predictive biomarkers.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788237","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}

{"title":"Paediatric therapeutic development workshop on osteosarcoma.","authors":"Joseph S Baxter, Claudia Montiel Equihua, Jan J Molenaar, Pablo Berlanga, Michael W Bishop, Patricia Blanc, Quentin Campbell-Hewson, Michela Casanova, Isidro Cortes-Ciriano, Brian Crompton, Sam Daems, Laura Danielson, Filemon Dela Cruz, Adrienne Flanagan, Richard Gorlick, Ann Graham, Lillian M Guenther, Stefanie Hecker-Nolting, Lee Helman, Maia Kavanagh-Williamson, Pamela Kearns, Geffen Lass, Christina Ip-Toma, John Ligon, Jeremy Lewin, J Andrew Livingston, Antonin Marchais, Martin G McCabe, Sybille Mittnacht, Michaela Nathrath, Emanuela Palmerini, Pan Pantziarka, Seema Patel, Sheena Patel, Damon Reed, Ryan Roberts, Katia Scotlandi, Emily Slotkin, Mandy Tseng, Walker Smallwood, Poul H Sorensen, Claudia Valverde, Madina Wane, Gemma A Wilson, Andrew D J Pearson, David Jenkinson, Nathalie Gaspar, Sandra J Strauss","doi":"10.1038/s41416-026-03572-1","DOIUrl":"https://doi.org/10.1038/s41416-026-03572-1","url":null,"abstract":"<p><p>The fourth Paediatric Therapeutic Development Workshop focused on osteosarcoma, the most common primary bone cancer in children and young adults. Current treatment of osteosarcoma comprises surgery and chemotherapy. Outcome has shown very little improvement over the last four decades and there are substantial unmet needs including improving survival, especially in metastatic or relapsed disease, and reducing treatment toxicity. There is a lack of new therapeutics in osteosarcoma, with the evaluation of new treatments challenged by complex biology and variation in chemotherapy standard of care regimens. An antibody-drug conjugate (ADC) targeting LRRC15 with an osteosarcoma-relevant payload is a promising therapeutic approach. Small molecule inhibitors and degraders targeting SMARCAL1 should be considered as a very high priority, as it is a target applicable to several high unmet need malignancies. Preclinical evaluation of KIF18A in osteosarcoma models is required. An early phase study of an eIF4A1 inhibitor is warranted. Further preclinical validation of RUNX2 using PROTACs or ADCs is required. Targeting MYC, either indirectly or directly is a high priority. Osteosarcomas have significant genomic instability and impaired DNA repair mechanisms and efforts are ongoing to exploit this vulnerability therapeutically. The goal is that these therapeutic developments will improve survival for patients with osteosarcoma.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788254","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}

{"title":"CTPS1 promotes lung adenocarcinoma progression as a targetable vulnerability.","authors":"Hui Xie, Caixia Xu, Binghan Zhou, Fang Cheng, Hongliang Xu, Wencheng Zhang, Xuejun Shi, Wenhao Shi, Dongdong Zhan, Guangshun Wang","doi":"10.1038/s41416-026-03580-1","DOIUrl":"https://doi.org/10.1038/s41416-026-03580-1","url":null,"abstract":"<p><strong>Background: </strong>Cytidine triphosphate synthase 1 (CTPS1), a rate-limiting enzyme in nucleotide biosynthesis, is frequently upregulated in cancers. However, its functional role and therapeutic potential in lung adenocarcinoma (LUAD) remain poorly defined.</p><p><strong>Methods: </strong>We integrated proteomic analyses, tissue microarrays, and functional assays to evaluate CTPS1 expression and clinical significance in LUAD. Genetic knockdown and pharmacological inhibition with the selective inhibitor STP938 assessed malignant phenotypes. The therapeutic efficacy of STP938, alone or combined with osimertinib, was evaluated in xenograft models. Integrated proteomic and transcriptomic analyses explored underlying mechanisms.</p><p><strong>Results: </strong>CTPS1 was significantly upregulated in LUAD and associated with lymph node metastasis and poor overall survival (OS), serving as an independent prognostic factor. CTPS1 promoted proliferation, migration, and invasion while suppressing apoptosis. STP938 inhibited tumour growth in vitro and in vivo, and enhanced the efficacy of osimertinib in EGFR-mutant models. Multi-omics analyses identified MX1-associated interferon signalling as a downstream pathway, with MX1 expression positively correlating with CTPS1 and poor prognosis.</p><p><strong>Conclusions: </strong>CTPS1 drives LUAD progression and is linked to MX1-associated interferon signalling. Targeting CTPS1 with STP938, alone or in combination with osimertinib, represents a promising therapeutic strategy and supports CTPS1 as a targetable vulnerability in LUAD.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788298","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}

{"title":"Retraction Note: Antitumour activity of the recombination polypeptide GST-NT21MP is mediated by inhibition of CXCR4 pathway in breast cancer","authors":"Q. Yang,&nbsp;F. Zhang,&nbsp;Y. Ding,&nbsp;J. Huang,&nbsp;S. Chen,&nbsp;Q. Wu,&nbsp;Z. Wang,&nbsp;Z. Wang,&nbsp;C. Chen","doi":"10.1038/s41416-026-03584-x","DOIUrl":"10.1038/s41416-026-03584-x","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 7","pages":"1181-1181"},"PeriodicalIF":7.8,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03584-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in urinary biomarkers for endometrial cancer detection.","authors":"Molly Dore, Jiexin Cao, Holly Baker-Rand, Ananya Choudhury, Anthony D Whetton, Richard D Unwin, Emma J Davidson, Kelechi Njoku","doi":"10.1038/s41416-026-03579-8","DOIUrl":"https://doi.org/10.1038/s41416-026-03579-8","url":null,"abstract":"<p><p>The incidence of endometrial cancer is rising globally, placing significant burden on diagnostic pathways for women with abnormal uterine bleeding. Current evaluation relies primarily on transvaginal ultrasound followed by invasive endometrial visualisation and sampling, although most symptomatic women have no sinister underlying pathology. Urine offers a promising non-invasive and easily repeatable biofluid capable of capturing tumour-associated signals through both systemic renal filtration and locally shed uterine material. This review summarises emerging evidence on urinary biomarkers for endometrial cancer detection, including somatic mutations, DNA methylation markers, proteins and peptides, vibrational spectroscopy signatures, microRNAs, metabolites and urine cytology. These biomarkers collectively reflect key biological processes driving endometrial carcinogenesis, including hormonal and metabolic dysregulation, immune activation, epithelial-stromal disruption, cellular proliferation and genomic instability. Among current candidates, DNA methylation panels and mutation-based assays have demonstrated encouraging diagnostic performance, with studies reporting sensitivities and specificities exceeding 80-90% in symptomatic populations. Urine cytology also shows strong diagnostic potential in selected cohorts, while metabolomic, proteomic and spectroscopy-based approaches remain promising but require further standardisation and prospective validation. Although not yet suitable for population screening, urinary biomarkers show considerable potential for risk stratification and triage of symptomatic women, potentially reducing unnecessary invasive investigations. Clinical translation will require standardised protocols, multi-centre validation and integration into existing diagnostic pathways.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711375","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}

{"title":"Exploring PDLIM2 as a prognostic biomarker and therapeutic target in lung adenocarcinoma.","authors":"Karam Ashouri, Fan Sun, Harris Krause, Andrew Elliott, Stephen V Liu, Patrick C Ma, Balazs Halmos, Gutian Xiao, Ari Vanderwalde, Jorge J Nieva, Zhaoxia Qu","doi":"10.1038/s41416-026-03570-3","DOIUrl":"10.1038/s41416-026-03570-3","url":null,"abstract":"<p><strong>Background: </strong>While PDZ-LIM domain-containing protein (PDLIM2) suppresses lung cancer, its clinical significance and therapeutic potential remain to be fully explored.</p><p><strong>Methods: </strong>Next-generation sequencing and immunohistochemistry of programmed death ligand 1 (PD-L1) were performed on lung adenocarcinoma (LUAD) tissues from 15,765 patients. PDLIM2 gene therapy was tested in syngeneic LUAD mouse models using intravenous nano-complexed plasmid DNA, alone or with chemoimmunotherapy.</p><p><strong>Results: </strong>PDLIM2-high tumors were more common in primary/local biopsies versus metastatic samples (73.1% vs 53.0%; p < 0.001). High PDLIM2 expression was linked to lower mutation rates in RB1, TP53, SMARCA4, STK11, and KEAP1, but increased EGFR mutations (all p < 0.01). PDLIM2-high tumors also showed increased immune cell infiltration, T cell-inflamed scores, and PD-L1 positivity (all p < 0.008). High PDLIM2 was associated with improved survival (24.1 vs 18.1 months; p < 0.001, HR = 0.84) and remained prognostic in multivariate analysis (HR = 0.88, 95% CI 0.83-0.93), as well as with longer pembrolizumab time, especially with platinum-based therapy (p = 0.012, HR = 0.867). In two LUAD mouse models, nanoPDLIM2 improved median overall survival versus chemoimmunotherapy alone (10-12.5 vs 8-9 days; N = 8; p = 0.0001, 0.0003).</p><p><strong>Conclusion: </strong>PDLIM2 is a promising prognostic biomarker in LUAD linked to immune-receptive tumors. Preclinically, PDLIM2-based therapy enhances chemoimmunotherapy efficacy, though its predictive role warrants further evaluation.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148696953","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}

{"title":"The effect of cigar, cigarillo and pipe smoking on lung cancer risk and screening eligibility.","authors":"Simran Vaja, Jennifer L Dickson, Carolyn Horst, Monica L Mullin, Amyn Bhamani, Andrew Creamer, Helen Hall, Chuen R Khaw, Ruth Prendecki, Priyam Verghese, Sophie Tisi, John McCabe, Esther Arthur-Darwka, Neal Navani, Anand Devaraj, Arjun Nair, Sam M Janes, Allan Hackshaw","doi":"10.1038/s41416-026-03578-9","DOIUrl":"https://doi.org/10.1038/s41416-026-03578-9","url":null,"abstract":"<p><strong>Background: </strong>Smokers are eligible for lung cancer screening using low dose CT (LDCT) if they have a sufficiently high risk of lung cancer. In England, for example, people are eligible if their estimated risk using either of two validated models (PLCO_m2012 and Liverpool Lung Project) exceeds a certain threshold. Risk is often estimated using only cigarette consumption (duration and number per day), yet many smokers also use other cancer-causing tobacco products.</p><p><strong>Methods: </strong>SUMMIT is a prospective cohort study of a LDCT screening service. We evaluated the impact of cigars, pipes, and cigarillos on lung cancer risk.</p><p><strong>Results: </strong>Among 13,000 participants who were current/former cigarette smokers, 511 (1 in 25) were also regular users of cigars, pipes, or cigarillos. The 5-year cumulative lung cancer incidence in people who currently smoked both types of tobacco products was 8.85%, versus 5.74% for cigarette only current smokers. Among these 511 participants, the percentage whose risk was below the screening eligibility threshold ignoring other tobacco products which then exceeded the threshold including these products was 0.6% using LLPv2, and 8.2% using PLCO_m2012.</p><p><strong>Conclusions: </strong>All tobacco consumption should be considered when determining screening eligibility to avoid missing those who can benefit from LDCT.</p><p><strong>Clinical trial registration: </strong>Clinicaltrials.gov no: NCT03934866.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688528","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}

{"title":"Editorial Expression of Concern: Growth inhibition and differentiation of human breast cancer cells by the PAFR antagonist WEB-2086","authors":"C. Cellai,&nbsp;A. Laurenzana,&nbsp;A. M. Vannucchi,&nbsp;R. Caporale,&nbsp;M. Paglierani,&nbsp;S. Di Lollo,&nbsp;A. Pancrazzi,&nbsp;F. Paoletti","doi":"10.1038/s41416-026-03582-z","DOIUrl":"10.1038/s41416-026-03582-z","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 6","pages":"1017-1017"},"PeriodicalIF":7.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03582-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}