British Journal of Cancer最新文献

{"title":"Cost-effectiveness of CA125- and age-informed risk-based triage for ovarian cancer detection in primary care.","authors":"Runguo Wu, Kirsten D Arendse, Tooba Hamdani, Fiona M Walter, Emma J Crosbie, Borislava Mihaylova, Garth Funston","doi":"10.1038/s41416-025-03166-3","DOIUrl":"https://doi.org/10.1038/s41416-025-03166-3","url":null,"abstract":"<p><strong>Background: </strong>In England, current practice is cancer antigen 125 (CA125) testing with pelvic ultrasound scan (USS) if CA125 is ≥35 U/mL for triage of women with suspected ovarian cancer (OC) in primary care. However, OC risk varies with CA125 level and age. The Ovatools model predicts OC risk based on age and CA125 levels to support primary care triage.</p><p><strong>Methods: </strong>We evaluated five alternative triage pathways for suspected OC in primary care, using a decision model. Two CA125-USS sequential pathways used Ovatools risk: 1-3% (subsequent USS) and ≥3% (urgent referral), or age-adjusted CA125 thresholds equivalent to Ovatools risks. Three pathways involved concurrent CA125-USS testing, with referral if abnormal USS or one of the following: (1) Ovatools risk ≥3%, (2) CA125 above the equivalent age-adjusted threshold, or (3) CA125 ≥ 35 U/mL. Clinical and cost-effectiveness was compared against current practice for women over and under 50 years.</p><p><strong>Results: </strong>All alternative pathways increased benefits at age ≥50 years, at additional cost. The incremental cost-effectiveness ratios for CA125-USS sequential pathways were below £30,000, dropping below £20,000 if the Ovatools threshold for USS increased to 1.2-1.4% risk.</p><p><strong>Discussion: </strong>For women ≥50 years, the Ovatools and equivalent age-adjusted threshold sequential pathways are cost-effective compared to current practice.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079450","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":"Methodological reasons for the low prevalence of human papillomavirus infection in progressors versus non-progressors from Barrett's oesophagus to oesophageal adenocarcinoma.","authors":"Shanmugarajah Rajendra, Mohammad Rabiei","doi":"10.1038/s41416-025-03187-y","DOIUrl":"https://doi.org/10.1038/s41416-025-03187-y","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079444","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":"Serum lipid levels and risk of lymphoid malignancies in the UK Biobank study.","authors":"Sara Hermosa, Yolanda Benavente, Elena Cabezudo, Juan Sainz, Marta Farràs, Laia Alemany, Brenda M Birmann, Delphine Casabonne","doi":"10.1038/s41416-025-03196-x","DOIUrl":"https://doi.org/10.1038/s41416-025-03196-x","url":null,"abstract":"<p><strong>Background: </strong>Abnormal circulating lipid levels have been suggested in relation to lymphoid malignancy (LM) risk.</p><p><strong>Methods: </strong>We studied UK Biobank participants (n = 403,625) with serum data for cholesterol (total [TC], high-density lipoprotein [HDL], direct low-density lipoprotein [LDL]), triglycerides (TG), and apolipoproteins A1 and B (ApoA1, ApoB). We conducted principal component (PC) analysis and multivariate Cox regression models to estimate hazard ratio (HR) overall, by lipid-lowering drug use and follow-up interval.</p><p><strong>Results: </strong>During an average of 10.5 years of follow-up, 3006 incident LMs occurred (including 667 multiple myelomas [MM], 2193 non-Hodgkin lymphomas [NHL]). Among medication non-users, most lipid levels were inversely associated with risk of most endpoints (HR_Q4vsQ1range: 0.37 to 0.79), especially closer to diagnosis. In contrast LDL/HDL ratio and PC1 (highly loaded in LDL and ApoB) were consistently positively associated with chronic/small lymphocytic leukaemia risk in each follow-up period and with NHL and B-cell NHL risk within 5 years. Further, LD, ApoB and TG levels were positively associated with MM risk after 10+ years (HR_1-SDrange = 1.26 to 1.60).</p><p><strong>Conclusion: </strong>Lipid depletion closer to LM diagnosis might reflect cancer cell metabolism and warrants further work examining individuals with precursor conditions. The MM-specific long-term risk might reflect the known MM-obesity association.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079611","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":"Deciphering the central role of TMOD2 in colorectal cancer progression and metastasis.","authors":"Ana Montero-Calle, Sofía Jiménez de Ocaña, Raquel Rejas-González, Ruth Benavente-Naranjo, Rodrigo Sanz-López, Jana Dziaková, Javier Martínez-Useros, Alberto Peláez-García, Vivian de Los Ríos, Rubén A Bartolomé, J Ignacio Casal, María Jesús Fernández-Aceñero, Rodrigo Barderas","doi":"10.1038/s41416-025-03184-1","DOIUrl":"https://doi.org/10.1038/s41416-025-03184-1","url":null,"abstract":"<p><p>Tropomodulin-2 (TMOD2) is upregulated in the nuclear compartment of highly liver metastatic colorectal cancer (CRC) cells. Its role in cancer and CRC progression is functionally undefined, despite its analysis in COAD and READ TCGA datasets revealing a correlation between high TMOD2 expression, advanced disease stages, and poorer survival in CRC patients. We aimed here to explore the role of TMOD2 in CRC and liver metastasis using functional proteomics, tumour samples, bioinformatics, and in vitro and in vivo CRC models. Stable overexpression and stable depletion of TMOD2 in isogenic CRC cells revealed its impact on tumorigenic and metastatic properties. TMOD2 overexpression enhanced cell adhesion, anchorage-independent growth, and migration, while stably TMOD2 depletion reduced them. In vivo, TMOD2-overexpressing cells formed larger tumours and enhanced liver colonisation of CRC cells. Clinically, TMOD2 protein levels demonstrated strong discriminatory ability between metastatic and non-metastatic CRC patients. Proteomic analyses allowed the identification of TMOD2-associated proteins involved in cytoskeletal dynamics, secretion, and focal adhesions, with further validation implicating STAG1 and MARCKS as mediators of TMOD2-driven pathways. Our findings demonstrate that TMOD2 plays a role in CRC progression by modulating cytoskeletal dynamics, enhancing cell adhesion and promoting liver metastasis, positioning TMOD2 as a target for therapeutic intervention in CRC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079443","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":"CA125 and age-based models for ovarian cancer detection in primary care: a population-based external validation study.","authors":"Kirsten D Arendse, Fiona M Walter, Gary Abel, Brian Rous, Willie Hamilton, Emma J Crosbie, Garth Funston","doi":"10.1038/s41416-025-03165-4","DOIUrl":"https://doi.org/10.1038/s41416-025-03165-4","url":null,"abstract":"<p><strong>Background: </strong>Cancer antigen-125 (CA125) is widely used to investigate symptoms of possible ovarian cancer (OC) in primary care. However, OC risk varies with age and CA125 level. We externally validated the Ovatools models, which provide CA125- and age-specific OC risk.</p><p><strong>Methods: </strong>The performance of Ovatools in predicting OC diagnosis within 12 months of primary care CA125 was examined using English healthcare data for women <50 and ≥50 years. Discrimination and calibration were examined, accuracy was calculated at varying risk thresholds and compared to CA125 ≥ 35U/ml. We estimated OCs missed/detected by Ovatools in hypothetical diagnostic pathways, including a two-threshold pathway where moderate risk (1-2.9%) triggered primary care ultrasound, and higher risk (≥3%) triggered urgent cancer referral.</p><p><strong>Results: </strong>342,278 women were included, 0.63% had OC. The AUC was 0.95 in women ≥50 and 0.89 in women <50. When sensitivity/specificity were matched to CA125 ≥ 35U/ml, Ovatools showed marginally improved performance across other accuracy metrics in women ≥50 years. In a two-threshold pathway (≥50 years), 18.3% identified for urgent referral and 1% identified for ultrasound had OC.</p><p><strong>Discussion: </strong>Ovatools performed well on external validation. Ovatools could be used to support informed decision-making and to triage women for further investigation based on cancer risk.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079367","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":"Exercise oncology in prostate cancer: from observational insight to prescriptive precision.","authors":"Matthias May, Christian Gilfrich, Benazir Enzinger, Sabine Brookman-May","doi":"10.1038/s41416-025-03205-z","DOIUrl":"10.1038/s41416-025-03205-z","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074362","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":"Single-cell multiomic modelling of early metastatic events promoted by the extracellular matrix.","authors":"Hyun Jin Lee, Jun Hyeong Lee, Junho Kang, Kyeonghui Kim, Youngwon Cho, Jihyun Park, Sang-Hyun Song, Joonha Kwon, Young-Joon Kim, Woong-Yang Park, Tae-You Kim, Jong-Eun Park, Pilnam Kim, Jung Kyoon Choi","doi":"10.1038/s41416-025-03181-4","DOIUrl":"https://doi.org/10.1038/s41416-025-03181-4","url":null,"abstract":"<p><strong>Background: </strong>Cancer metastasis, primarily driven by epithelial-to-mesenchymal transition (EMT), is responsible for most cancer-related mortalities. Traditional pre-clinical models fail to fully capture mesenchymal characteristics due to the loss of human stroma. The extracellular matrix (ECM) plays a crucial role in EMT, yet conventional in vitro models often rely on defined ECM components, which may not adequately replicate the human physiological ECM niche.</p><p><strong>Methods: </strong>To mimic the in situ dissemination of cancer cells, we employed a patient-derived extracellular matrix (pdECM). We transitioned the culture matrix for patient-derived colorectal cancer organoids from a basement membrane extract (BME) to a patient-derived ECM (pdECM). We performed single-cell multiomic analyses, integrating transcriptomic and epigenomic data, to investigate changes in organoid phenotypes and reconstruct the EMT trajectory.</p><p><strong>Results: </strong>Organoids cultured in the pdECM exhibited increased tumor cell dissemination and motility, resembling in situ lesions without exogenous ligand treatment. Single-cell multiomic analysis revealed TNF-α signaling as an early metastatic event in the EMT trajectory. Epigenomic changes led to increased accessibility of AP-1 complex target genes, particularly MMP7, which promoted an invasive phenotype. Our multimodal computational approach distinguished early and late EMT states, demonstrating that pdECM-induced EMT occurs independently of traditional EMT master regulators. Notably, pdECM organoids exhibited a partial EMT phenotype, characterized by hybrid epithelial-mesenchymal states.</p><p><strong>Conclusion: </strong>This study presents an advanced in vitro model that closely recapitulates in situ tumorigenesis and provides novel insights into the metastatic cascade. The pdECM system enables the reconstruction of EMT dynamics, highlighting the critical role of ECM composition in metastasis and offering a physiologically relevant platform for the development of targeted therapies.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069158","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":"Integrative proteo-genomic profiling uncovers key biomarkers of lapatinib resistance in HER2-positive breast cancer.","authors":"J Steggall, V Rajeeve, N Al-Subaie, A Naeem, A Ikram, A Naeem, A Hayat","doi":"10.1038/s41416-025-03174-3","DOIUrl":"https://doi.org/10.1038/s41416-025-03174-3","url":null,"abstract":"<p><strong>Introduction: </strong>Drug resistance is a major obstacle to the long-term effectiveness of cancer therapies. Approximately 70% of breast cancer patients relapse after 5 years of treatment, and the lack of biomarkers associated with drug resistance translates to poor prognosis in the clinic. Previous research has utilised omics approaches to uncover biomarkers driving drug resistance, with a strong emphasis on genetic mutations.</p><p><strong>Methods: </strong>Here, we identified a nine-marker signature associated with resistance to lapatinib in a HER2-positive breast cancer model using a target discovery approach by employing an integrative multi-omics strategy, combining ATAC-seq, RNA-seq and proteomics.</p><p><strong>Results: </strong>We found that seven markers in the drug resistance-signature had not been previously found to be implicated in HER2-positive breast cancer, some of which we further validated using an additional lung cancer model. We counterintuitively found that drug-resistant cells have restrictive chromatin accessibility with reduced gene expression associated with limited total proteome changes. However, upon closer look, we identified that the drug resistance-signature had increased chromatin accessibility near the transcriptional start sites of those seven markers and was highly differentially expressed across the three datasets. Our data show that despite the overall transcriptional and proteomic landscape showing limited changes, there are several markers that are highly expressed, which correlate with increased anchorage-independent and invasive phenotype in vitro in lapatinib-resistant cells compared to cancer cells.</p><p><strong>Conclusions: </strong>Our results demonstrate that disease aggressiveness can be related to reduced chromatin and gene expression dynamics. We anticipate that the resistant signature identified here using an integrative target discovery approach can be applied to complex, more representative models and validated before they can be targeted by suitable therapeutic agents.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058336","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":"Acceptance of external control arms by HTA agencies: a review of oncology submissions in France, England, Germany and Norway from 2021 to 2023.","authors":"Matthias Monnereau, Jean-Pierre Delord, Stefan Michiels, Christophe Le Tourneau, Sebastien Marque, Louise Baschet, Thomas Filleron","doi":"10.1038/s41416-025-03155-6","DOIUrl":"https://doi.org/10.1038/s41416-025-03155-6","url":null,"abstract":"<p><strong>Purpose: </strong>External control arms (ECAs) are sometimes considered as an alternative to phase III trials, enabling comparisons without head-to-head trials. Deploying ECAs is complex, partially due to varying regulatory guidelines. We aimed to assess their acceptance in oncology by Health Technology Assessment (HTA) bodies across France, England, Germany, and Norway from 2021 to 2023.</p><p><strong>Methods: </strong>We conducted a review of HTA evaluation reports for oncology treatments using ECAs. Reports were extracted from national HTA body websites and systematically reviewed. Data extraction included drug characteristics, ECA methodology, acceptance status, and reported issues. ECAs were categorized by type of data: Individual Patient Data (IPD), Aggregated Data (AgD), or naive comparisons.</p><p><strong>Results: </strong>We analysed 175 ECAs from 123 reviews, none were accepted without restrictions, and only 17% were not rejected. Acceptance rates varied significantly between countries, with England showing the highest non-rejection rate (accepted with restrictions) (41%), followed by France (14%) while Germany and Norway rejected all ECAs. The main methodological issues identified were lack of/unclear data (54%), heterogeneity between studies or risk of bias (51%), study design concerns (29%), and statistical methodology limitations (26%). These challenges were consistent across different types of ECAs, though their relative importance varied by country.</p><p><strong>Conclusions: </strong>Despite the increasing use of ECAs in oncology trials, their acceptance by HTA bodies remains limited. Our findings highlight significant disparities in assessment approaches between countries and persistent challenges in data quality and methodological consistency. Future efforts should focus on improving transparency, robustness, and residual bias assessment of ECA methodologies.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051841","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":"Italian guidelines for cervical cancer screening. Multisocietal recommendations on the use of biomarkers in HPV screening with risk-based approach and GRADE methodology.","authors":"Silvia Gori, Francesco Venturelli, Francesca Carozzi, Paolo Giorgi Rossi, Annarosa Del Mistro","doi":"10.1038/s41416-025-03161-8","DOIUrl":"https://doi.org/10.1038/s41416-025-03161-8","url":null,"abstract":"<p><p>The European Council recommends adopting risk-based screening when relevant. In triaging HPV-positive women, it can be an effective strategy to reduce overtreatment and referral to colposcopy. HPV genotyping and p16/ki67 expression may allow a better risk stratification than cytology. In Italy, recommendations on their use (alone or combined) in screening were developed by a multi-professional (nine scientific societies) and multidisciplinary working group (including patients and decision makers). Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision frameworks were used. Data from large clinical trials on screening populations with long follow-up instructed the biomarkers' evaluation. The working group defined the CIN3+ risk thresholds (a surrogate marker of cancer risk) to guide decisions on management: immediate colposcopy, referral to 1-year and 3-year retesting. The risk-based approach allowed to reduce the number of possible strategies to be compared to five specific healthcare questions framed as PICOs. The prioritised outcomes were risk of cancer and of CIN3+ in HPV+/triage-negative women, number of colposcopies, number of samples to be taken, and number of unneeded treatments. The combination of morphological markers (cytology or p16/ki67) and extended HPV genotyping was the only strategy with a conditional recommendation in favour when compared with cytology.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032708","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}