British Journal of Cancer最新文献

{"title":"Refining treatment strategies for non-small cell lung cancer lacking actionable mutations: insights from multi-omics studies.","authors":"Andrea Rocca, Lucio Crinò, Luca Braga, Francesco Salton, Barbara Ruaro, Marco Confalonieri, Daniele Generali, Paola Confalonieri","doi":"10.1038/s41416-025-03139-6","DOIUrl":"https://doi.org/10.1038/s41416-025-03139-6","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) represents a heterogeneous group of malignancies characterised by diverse histological and molecular features. Some NSCLCs, particularly adenocarcinomas, harbour genomic alterations in receptor tyrosine kinases or downstream RAS/RAF signalling pathways, which are targets of effective therapies. NSCLCs lacking actionable genomic alterations often benefit from immune checkpoint inhibitors, though only a minority of patients achieve long-term survival. These tumours often carry alterations in tumour suppressor genes like TP53, KEAP1, STK11, or NF1, for which pharmacological strategies are still under investigation. This review explores emerging therapeutic opportunities unveiled by multi-omics studies in NSCLCs without actionable genomic alterations. Proteogenomic approaches-integrating genomic, transcriptomic and proteomic data-enable a comprehensive understanding of NSCLC molecular landscapes and signalling network dysregulation, helping to identify distinct tumour subtypes and potential therapeutic targets. These tumours exhibit alterations in cell cycle regulation, DNA repair, immune signalling, epigenetic modulation and metabolic and redox pathways. Although therapies targeting tumour suppressor genes like p53 remain highly anticipated, extending our understanding of the broader molecular landscape in these tumours may reveal novel vulnerabilities and inform the development of novel drugs or combination strategies. This could further advance precision oncology for NSCLC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943394","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":"Capturing breast cancers' copy-number landscape in routine pathology: Exploiting low-resolution, genome-wide sequencing to identify HRD and beyond.","authors":"C J H Kramer, L M van Wijk, D Ruano, S Gelpke-Vermeulen, K van der Tuin, N van der Stoep, T van Wezel, J Wesseling, J Vallon-Christersson, V T H B M Smit, D Cohen, H Vrieling, J Staaf, T Bosse, C J van Asperen, M P G Vreeswijk","doi":"10.1038/s41416-025-03134-x","DOIUrl":"https://doi.org/10.1038/s41416-025-03134-x","url":null,"abstract":"<p><strong>Background: </strong>Because breast cancer (BC) is molecularly heterogeneous, diagnosis and treatment will likely benefit from comprehensive genetic profiling. However, routine, high-resolution sequencing is not feasible yet, due to implementation challenges associated with whole-genome sequencing of formalin-fixed paraffin embedded (FFPE) BC samples. Therefore, we explored the potential of an alternative low-resolution, genome-wide testing approach that is able to capture the copy number (CN) landscape, including actionable alterations, in FFPE derived DNA.</p><p><strong>Methods: </strong>The performance of the genome-wide CN testing approach, including CN signatures/focal CN alterations, was evaluated in two phases: (i) exploration and (ii) feasibility phase. First, high-resolution sequencing data of a previously published triple-negative BC cohort (n = 237) was leveraged to benchmark the homologous recombination deficiency (HRD)-related CN signature using a comprehensive, multimodal approach incorporating both genetic and functional HRD tests. Secondly, the low-resolution testing strategy's feasibility was prospectively evaluated in a BC cohort of patients referred to clinical genetic services (n = 147).</p><p><strong>Results: </strong>Applying the HRD threshold that was established using both genomic and functional HRD data, we identified a 100% sensitivity for BC with BRCA1/BRCA2/PALB2 pathogenic variants in the prospective cohort. Moreover, the success rate of the low-resolution testing approach proved high, regardless of input material. Finally, additional CN alterations were enriched in the HR-proficient BC population, indicating potential actionable CN-alterations beyond HRD.</p><p><strong>Conclusions: </strong>In conclusion, low-resolution, genome-wide sequencing has shown high potential in capturing the CN landscape, including features associated with HRD, in BC patients. This preselection testing approach is likely to maximize potential for personalized medicine and genetic counseling.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943678","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 diagnostic accuracy of the faecal immunochemical test for the detection of early-onset colorectal cancer: an age-stratified analysis in South West England.","authors":"Melissa Barlow, David Messenger, Ryan Preece, Amy Prowse, Gary Abel, Willie Hamilton, Samuel Wd Merriel, Adam Chambers, Sarah Er Bailey","doi":"10.1038/s41416-025-03154-7","DOIUrl":"https://doi.org/10.1038/s41416-025-03154-7","url":null,"abstract":"<p><strong>Background: </strong>The incidence of early-onset colorectal cancer (EOCRC) is rising rapidly, with diagnoses typically occurring at a more advanced stage than late-onset CRC. In the absence of screening for younger patients, diagnosis relies on symptomatic presentation. The faecal immunochemical test (FIT) is a diagnostic triage tool for patients presenting with clinical features of CRC in primary care, though its performance in individuals under 50 years is not well established.</p><p><strong>Methods: </strong>A cohort of 38,117 symptomatic patients aged 18-49 years in upper South West England underwent FIT in primary care between 01/01/2021 and 10/07/2023. A FIT result of ≥10 µg Hb/g faeces was considered positive. In the same region, 528 EOCRC diagnoses were recorded between 01/01/2021 and 10/10/2024.</p><p><strong>Results: </strong>Of the 528 EOCRC patients, 105 (20%) underwent FIT in the year before diagnosis. The sensitivity of FIT was 92.4% (95% CI 85.5-96.7%), specificity was 88.5% (88.2-88.8%), positive predictive value (PPV) was 2.2% (1.8-2.6%), and negative predictive value was 100% (100-100%). PPVs decreased in younger age groups (18-29, 30-39, 40-49 years).</p><p><strong>Conclusions: </strong>FIT performs excellently for patients aged 40-49; however, it may not be used optimally in patients <40 years. A more targeted strategy is needed to guide investigation in younger patients.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943510","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 novel role of DUSP4 in suppressing ferroptosis and promoting cytotoxicity of CD8⁺ T cells in MSI colorectal cancer.","authors":"Dongsheng Zhang, Sheng Yang, Hengjie Xu, Zhihao Chen, Xiaowei Wang, Yueming Sun","doi":"10.1038/s41416-025-03119-w","DOIUrl":"https://doi.org/10.1038/s41416-025-03119-w","url":null,"abstract":"<p><strong>Background: </strong>Microsatellite instable (MSI) colorectal cancer (CRC) has distinct features that distinguish it from microsatellite stable CRC. While ferroptosis may play a role in the development of MSI CRC, its mechanisms remain unclear.</p><p><strong>Methods: </strong>Ferroptosis was assessed via the detection of lipid peroxidation, malondialdehyde, 4-hydroxy-2-nonenal, and intracellular Fe2⁺, etc. Phosphoproteomic analysis, cytokine array, and flow cytometry were performed to explore the regulation of CD8⁺ T cell infiltration.</p><p><strong>Results: </strong>Dual specificity phosphatase 4 (DUSP4) suppressed ferroptosis in MSI CRC cells by reducing lipid peroxidation and inhibiting intracellular Fe2⁺ accumulation. Mechanistic studies showed that DUSP4 downregulated the expression of transferrin receptor (TFRC), which was transcriptionally regulated by c-MYC. In addition, a positive correlation was observed between the infiltration of CD8⁺ T cells in CRC tissues and the expression of DUSP4 in cancer cells. Mechanistically, DUSP4 dephosphorylated cyclin-dependent kinase 7 (CDK7) and promoted C-X-C Motif chemokine ligand 16 (CXCL16) expression, resulting in an increased infiltration of CD8⁺ T cells. Importantly, the combination of a CDK7 inhibitor and anti-programmed cell death protein-1 therapy demonstrated a synergistic therapeutic effect in MSI CRC.</p><p><strong>Conclusion: </strong>DUSP4 acts as a negative regulator of ferroptosis and a positive regulator of CD8⁺ T cell infiltration in MSI CRC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943561","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":"An intelligent diagnostic model for pulmonary nodules utilizing chest radiographic imagery and its application in community-based lung cancer screening.","authors":"Junxian Li, Ya Liu, Liwen Zhang, Yuchen Xing, Zhangyan Lyu, Yubei Huang, Pengyu Zhang, Zhaoxiang Ye, Meng Wang, Fengju Song","doi":"10.1038/s41416-025-03147-6","DOIUrl":"https://doi.org/10.1038/s41416-025-03147-6","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is a health threat, particularly in regions where advanced screening methods like LDCT are limited. In China, chest X-rays (CXRs) are the primary tool for early detection. Integrating AI can enhance CXR diagnostic accuracy, addressing current challenges in early lung cancer detection.</p><p><strong>Methods: </strong>We collected 4079 CXRs from 2518 individuals at TMUCIH. These were divided into a training set (1762 patients, 2965 images) and a validation set (756 patients, 1114 images). A deep learning (DL) model, based on the CXR-RANet architecture, was developed and validated using two external cohorts: 24,697 individuals (88,562 images) from the PLCO dataset and 4848 individuals from the ChestDR dataset. The model's performance was compared with mainstream DL algorithms and traditional machine learning (ML) model in feature extraction and classification.</p><p><strong>Results: </strong>In the TMUCIH dataset, 47.8% of patients had positive CXR results, compared to 3.9% in PLCO and 13.7% in ChestDR. The CXR-RANet model achieved an AUC of 0.933 in the internal validation set and 0.818 in the ChestDR dataset. In the PLCO dataset, it predicted lung cancer occurrence with AUCs of 0.902, 0.897, and 0.793 for 3, 5, and 10 years, respectively. The model outperformed mainstream DL algorithms in feature extraction and most ML algorithms in classification.</p><p><strong>Conclusion: </strong>The CXR-RANet presents a robust, scalable tool for diagnosing pulmonary nodules and lung cancer, enhancing the capabilities of community physicians in early detection and management, independent of expert experience. Its superior performance in feature extraction and classification underscores its value in lung cancer screening.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943676","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":"Correction: Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway","authors":"Nathalie C. Støer,&nbsp;Siri Vangen,&nbsp;Deependra Singh,&nbsp;Renée T. Fortner,&nbsp;Solveig Hofvind,&nbsp;Giske Ursin,&nbsp;Edoardo Botteri","doi":"10.1038/s41416-025-03038-w","DOIUrl":"10.1038/s41416-025-03038-w","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"133 6","pages":"910-911"},"PeriodicalIF":6.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-025-03038-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943654","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":"PROCC: a predictive score to identify KRAS wild type metastatic colorectal cancer patients who are likely to obtain survival benefit from panitumumab treatment.","authors":"Carlos María Galmarini, Rafael Zamora, Pablo Gómez Del Campo, José Del Castillo-Izquierdo, José Antonio De All, Juan Manuel Domínguez","doi":"10.1038/s41416-025-03157-4","DOIUrl":"https://doi.org/10.1038/s41416-025-03157-4","url":null,"abstract":"<p><strong>Background: </strong>Practice guidelines recommend panitumumab with chemotherapy to treat KRAS wild-type (WT) metastatic colorectal cancer (mCRC) patients. However, not all patients respond to this therapy. We propose a score termed \"PROCC\" to identify likely panitumumab responders.</p><p><strong>Methods: </strong>The training (TRDS) and validation (VALDS) datasets included KRAS WT mCRC patients treated with panitumumab (P) plus chemotherapy (TRDS, FOLFOX4; VALDS, FOLFIRI). TRDS included 36 diverse features used to generate synthetic representations analyzed via machine learning (ML) to identify patient subgroups, which were correlated with PFS and OS. A multivariable logistic regression model identified independent predictors to develop a predictive score.</p><p><strong>Results: </strong>ML identified two subpopulations in TRDS: SP-A (n = 162) and SP-B (n = 298). Only SP-A patients under P/FOLFOX4 showed improved OS versus FOLFOX4 (HR 0.68; p = 0.04). CEA, ALP, LDH, and platelets at baseline were used to create a predictive score (\"PROCC\"). For TRDS, the score had an area under the curve of 0.81. PROCC ≥8.5 correlated with lower risks of progression (HR 0.67; p = 0.03) and death (HR 0.65; p = 0.04) for P/FOLFOX4 versus FOLFOX4. Validation in VALDS confirmed similar results with FOLFIRI.</p><p><strong>Conclusions: </strong>Based on four baseline parameters, PROCC may guide the selection of KRAS WT mCRC patients most likely to benefit from panitumumab.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943246","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":"Anti-tumor activity of camptothecin analog conjugate of an RSPO4-based peptibody targeting LGR4/5/6 in preclinical models of colorectal cancer.","authors":"Yukimatsu Toh, Ling Wu, Jianghua Tu, Zhengdong Liang, Adela M Aldana, Jake J Wen, Li Li, Sheng Pan, Julie H Rowe, Martha E Hensel, Carolyn L Hodo, Rick A Finch, Kendra S Carmon, Qingyun J Liu","doi":"10.1038/s41416-025-03121-2","DOIUrl":"10.1038/s41416-025-03121-2","url":null,"abstract":"<p><strong>Background: </strong>Antibody-drug conjugates (ADCs) are a significant advancement in targeted cancer therapy, but none are approved for colorectal cancer (CRC). LGR4/5/6, highly expressed in most CRCs, are promising targets. While LGR5-targeting ADCs show strong anti-tumor effects, their efficacy is limited by LGR5 loss in some CRC cells. RSPO4, a natural ligand for LGR4/5/6, binds all three receptors with high affinity. This research develops RSPO4-based peptibody drug-conjugates (PDCs) to simultaneously target LGR4/5/6, offering a novel therapeutic approach for CRC.</p><p><strong>Methods: </strong>LGR4/5/6 expression in CRCs was analysed using RNA-seq datasets and Western blot. Peptibody binding affinities were measured, conjugated to camptothecin analog, CPT2, and tested for cytotoxicity in CRC cell lines. Antitumor efficacy was evaluated in vivo using CRC cell line and patient-derived xenograft (PDX) models.</p><p><strong>Results: </strong>Peptibody was engineered by fusing a mutant RSPO4 furin-domain to human IgG1 Fc, retaining high-affinity LGR4/5/6 binding without enhancing Wnt/β-catenin signalling. Conjugated with CPT2 molecules, the PDC showed strong antitumor activity in CRC cell lines and dose-dependent tumor growth inhibition in xenograft and patient-derived models.</p><p><strong>Conclusion: </strong>Preclinical data showed that LGR4/5/6-targeting PDC exhibited potent cytotoxicity in vitro and robust antitumor efficacy in CRC xenograft and PDX models, making its potential as a promising therapeutic approach for CRC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871588","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":"The lung immune prognostic index stratifies the occurrence of checkpoint inhibitor pneumonitis in advanced non-small cell lung cancer patients: a multi-institutional cohort study.","authors":"Bingxin Gong, Yusheng Guo, Qi Wan, Jie Lou, Guisheng Zhang, Yi Li, Feng Pan, Lian Yang","doi":"10.1038/s41416-025-03124-z","DOIUrl":"https://doi.org/10.1038/s41416-025-03124-z","url":null,"abstract":"<p><strong>Background: </strong>Lung immune prognostic index (LIPI) is associated with survival outcomes in patients with non-small cell lung cancer (NSCLC) receiving immunotherapy, but the association with the occurrence of checkpoint inhibitor pneumonitis (CIP) is unclear.</p><p><strong>Methods: </strong>We retrospectively included 1824 patients with advanced NSCLC who received immune checkpoint inhibitors (ICIs) at two institutions. Cox regression analysis and cumulative incidence curve were used to evaluate the predictive value of LIPI. Additionally, we performed competing risk analysis using Fine-Gray regression and cumulative incidence curves.</p><p><strong>Results: </strong>During a median follow-up of 15 months, 99 patients developed CIP. Compared with the good LIPI group, the intermediate LIPI group (HR 1.87, P = 0.007) and poor LIPI group (HR 4.39, P < 0.001) had a higher risk of CIP. Furthermore, we found LIPI was an independent predictor for intermediate-grade CIP (intermediate LIPI: HR 2.11, P = 0.056; poor LIPI: HR 4.51, P = 0.002) and high-grade CIP (intermediate LIPI: HR 6.94, P = 0.014; poor LIPI: HR 44.01, P < 0.001), but not for low-grade CIP (intermediate LIPI: HR 1.31, P = 0.392; poor LIPI: HR 0.72, P = 0.656). Similar results were obtained after competing risk analysis.</p><p><strong>Conclusions: </strong>LIPI grade shows potential in predicting the risk of CIP during immunotherapy and could be valuable in clinical management.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858930","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":"Correction: TIGIT antibody with PVR competitive ability enhances cancer immunotherapy and capable of eliciting anti-tumour immune memory","authors":"Huijuan Yu,&nbsp;Shaowen Jin,&nbsp;Min Zeng,&nbsp;Zhiqing Yang,&nbsp;Xiaofei Wang","doi":"10.1038/s41416-025-03084-4","DOIUrl":"10.1038/s41416-025-03084-4","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"133 6","pages":"909-909"},"PeriodicalIF":6.8,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-025-03084-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834068","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}