British Journal of Cancer最新文献

{"title":"PD-L1 expression and survival in unresectable/recurrent gastric cancer treated by 1st-line treatment without immune checkpoint inhibitors: JCOG1013A1.","authors":"Hidekazu Hirano, Yasuhide Yamada, Kengo Nagashima, Nobuyoshi Hiraoka, Shigeki Sekine, Naoki Takahashi, Mizutomo Azuma, Satoru Iwasa, Keisuke Kanato, Nozomu Machida, Takahiro Kinoshita, Hiroaki Hata, Hisato Kawakami, Daisuke Takahari, Toshiyasu Ojima, Shigenori Kadowaki, Narikazu Boku, Yukinori Kurokawa, Masanori Terashima, Takaki Yoshikawa","doi":"10.1038/s41416-026-03607-7","DOIUrl":"https://doi.org/10.1038/s41416-026-03607-7","url":null,"abstract":"<p><strong>Background: </strong>The prognostic significance of PD-L1 expression in unresectable/recurrent gastric cancer treated by first-line chemotherapy without an immune checkpoint inhibitor (ICI) remains unclear. The phase III trial JCOG1013 demonstrated no overall survival (OS) or progression-free survival (PFS) benefit of docetaxel/cisplatin/S-1 over cisplatin/S-1. This ancillary analysis of JCOG 1013 evaluated the prognostic value of PD-L1 expression.</p><p><strong>Methods: </strong>PD-L1 expression was assessed in pretreatment tumor specimens using the Dako 28-8 pharmDx assay. Combined positive score (CPS) and tumor proportion score (TPS) were calculated. PD-L1 positivity was defined as CPS ≥ 5 or TPS ≥ 1%. Univariable and multivariable analyses were performed for OS and PFS.</p><p><strong>Results: </strong>Among 741 patients enrolled in JCOG1013, 540 patients were included. In univariable analyses, neither CPS ≥ 5 nor TPS ≥ 1% was significantly associated with OS or PFS. In multivariable analyses, CPS ≥ 5 was not significantly associated with OS (HR 0.86, 95% CI 0.71-1.04; p = 0.127) or PFS (HR 0.92, 95% CI 0.77-1.11; p = 0.392); however, TPS ≥ 1% was significantly associated with longer OS (HR 0.78, 95% CI 0.62-0.97; p = 0.028) and PFS (HR 0.76, 95% CI 0.62-0.94; p = 0.012).</p><p><strong>Conclusions: </strong>TPS ≥ 1% is an independent favorable prognostic factor for survival in patients with unresectable/recurrent gastric cancer receiving chemotherapy alone.</p><p><strong>Clinical trial registration: </strong>UMIN000007652.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891030","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":"Radiomics as a spatial context for treatment decision-making in head and neck cancer.","authors":"Takeyuki Kono, Ken Kasahara, Ryo Ogawa, Hiroyuki Ozawa","doi":"10.1038/s41416-026-03600-0","DOIUrl":"https://doi.org/10.1038/s41416-026-03600-0","url":null,"abstract":"<p><p>Radiomics has been widely explored as a non-invasive biomarker in head and neck squamous cell carcinoma (HNSCC), yet its clinical role remains unclear. Tissue-based biomarkers differ in their susceptibility to spatial sampling. Biomarkers such as PD-L1 expression, immune-cell infiltration, necrosis, and immune exclusion may exhibit substantial spatial heterogeneity, whereas HPV/p16 status and some genomic alterations are generally more stable across the tumor. Nevertheless, localized sampling may incompletely capture heterogeneity in selected clinical contexts. This mismatch becomes clinically relevant when treatment decisions, particularly for chemoradiotherapy, immunotherapy, or de-escalation, are based on potentially non-representative biopsy findings. In this narrative review, we argue that the role of radiomics is not to outperform established biomarkers, but to contextualize them by capturing spatial heterogeneity related to hypoxia, necrosis, stromal architecture, and immune exclusion. We synthesize current evidence linking radiomic features to these biological processes and map them to specific clinical decision points, including larynx preservation, immunotherapy stratification, and recurrence assessment. Rather than serving as a standalone predictor, radiomics may provide complementary spatial information that helps identify situations in which biopsy-derived biomarkers should be interpreted with caution. Although current evidence is largely retrospective, radiomics offers a pragmatic framework for integrating spatial information into biomarker-guided clinical workflows.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886370","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":"Triglyceride enhancs NSCLC metastasis via lipid β-oxidation by RhoA-driven cytoskeletal remodeling in ECM-constrained microenvironments.","authors":"Yingchu Dai, Yufan Ling, Lu Hou, Tianqi Yang, Qianjiale Gu, Yiwen Fang, Wanshi Li, Hailong Pei, Leyuan Zhou","doi":"10.1038/s41416-026-03586-9","DOIUrl":"https://doi.org/10.1038/s41416-026-03586-9","url":null,"abstract":"<p><strong>Background: </strong>Elevated serum triglycerides (TG) are associated with poor prognosis in non-small cell lung cancer (NSCLC), but the mechanisms underlying this association remain unclear. Elucidating the role of TG in NSCLC metastasis may reveal novel therapeutic targets.</p><p><strong>Methods: </strong>A retrospective analysis was performed in 77 NSCLC patients stratified by serum TG levels. Survival was assessed using Kaplan-Meier analysis, and metastasis rates were compared using chi-square tests. Hypertriglyceridemia was modelled in mice. Extracellular matrix (ECM)-constrained invasion assays were conducted in NSCLC cell lines. Lipid β-oxidation and RhoA signalling were interrogated using pharmacological inhibition and genetic silencing of CPT1A and RhoA.</p><p><strong>Results: </strong>Patients with hypertriglyceridemia (TG > 2.3 mmol/L) had significantly shorter overall survival (log-rank p = 0.009) and higher rates of lymph node metastasis (84.4% vs. 37.9%) and distant metastasis (31.3% vs. 3.4%) than normotriglyceridemic patients (TG < 1.7 mmol/L). Mechanistically, TG enhanced lipid β-oxidation, activating RhoA-driven cytoskeletal remodelling that enabled tumour cells to overcome ECM confinement and acquire metastatic competence. Pharmacological inhibition or genetic silencing of CPT1A or RhoA significantly suppressed TG-induced invasion and metastasis.</p><p><strong>Conclusions: </strong>Elevated serum TG promotes NSCLC metastasis through a lipid β-oxidation-RhoA-cytoskeletal axis. Targeting lipid catabolism and cytoskeletal dynamics may represent a therapeutic strategy for hypertriglyceridemia-associated NSCLC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879147","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":"SLFN11 enhances cisplatin sensitivity in pediatric cancer via activation of stress-response and suppression of survival pathways.","authors":"Ayesha Jabeen, Dina Awartani, Shimaa Sherif, Eiman I Ahmed, Rania Alanany, Ayman Saleh, Wouter R L Hendrickx, Christophe M Raynaud","doi":"10.1038/s41416-026-03571-2","DOIUrl":"https://doi.org/10.1038/s41416-026-03571-2","url":null,"abstract":"<p><strong>Background: </strong>Paediatric cancers pose treatment challenges due to biological heterogeneity and variable chemotherapy responses. SLFN11, a DNA/RNA helicase-like protein known to sensitise adult tumours to DNA-damaging agents, remains underexplored in paediatric malignancies.</p><p><strong>Methods: </strong>We examined SLFN11 in Wilms tumour, osteosarcoma, and medulloblastoma using bioinformatics, epigenetic profiling and functional assays. Public datasets (TARGET, ICGC) were analysed to assess SLFN11 expression in relation to survival. Paediatric cancer cell lines were evaluated for baseline expression and promoter methylation. CRISPR-dCas9-mediated activation was used to restore SLFN11, and chemosensitivity was tested with cisplatin and the PARP inhibitor talazoparib. Transcriptomic profiling under cisplatin exposure was performed to identify pathways regulated by SLFN11.</p><p><strong>Results: </strong>SLFN11 showed tumour type-specific correlations with patient outcome, acting as a positive, negative, or neutral predictor depending on cancer context. Promoter methylation regulated SLFN11 expression in paediatric cancers similarly to adult tumours. SLFN11 activation sensitised all three functionally tested cell lines to cisplatin and talazoparib, with transcriptomics showing its role in DNA damage response and MAPK signalling to enhance chemotherapy cytotoxicity.</p><p><strong>Conclusion: </strong>In paediatric solid tumours, SLFN11 is a potential predictive biomarker of treatment response. Its ability to dictate the DNA damage landscape through epigenetic modulation highlights its significance as a target for overcoming chemoresistance and improving therapeutic efficacy in young patients. SLFN11 functions as a context-dependent biomarker of outcome and chemotherapy response in paediatric solid tumours. Its epigenetic regulation and modulation of DNA damage highlights SLFN11 as a therapeutic target to overcome chemoresistance.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879129","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":"Why early pathology input matters in biologically rich cancer trials.","authors":"Manas Dave, Maggie Chon U Cheang, Guy Betts, Tomoko Iwata, Michelle Frost, Chiara Braconi, Menna Shamma, Timothy J Kendall","doi":"10.1038/s41416-026-03605-9","DOIUrl":"https://doi.org/10.1038/s41416-026-03605-9","url":null,"abstract":"<p><p>Pathology is central to many biologically driven cancer clinical trials. Biomarker-led and translational studies depend on robust tissue pathways, cellular and molecular assays, pathology-derived endpoints, and clinically meaningful interpretation of discovery science. Where trials depend on tumour material, biomarker-defined eligibility or mechanism-focused endpoints, pathology expertise should be embedded early, before protocols, budgets, and assays are fixed. Early pathology input strengthens feasibility, specimen governance, assay selection, quality assurance, and the long-term value of collected samples. In the UK, the Clinical Trials Pathology Advisory Group, now within the new Pathological Society of Great Britain and Ireland Clinical Trials Pathology subcommittee, provides a practical route for pre-submission specialist review. This Perspective argues that pathology is core infrastructure for biologically rich trials, linking discovery science to clinical translation.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873205","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: Anti-PDGFRα autoantibody – a novel diagnostic and prognostic marker – may mediate non-small cell lung cancer progression via the PI3K/AKT/NF-κB signaling pathway","authors":"Fengqi Chen,&nbsp;Ying Chen,&nbsp;Wenke Sun,&nbsp;Hanke Ma,&nbsp;Yihao Liang,&nbsp;Yutong Li,&nbsp;Jing Li,&nbsp;Xiaobin Cao,&nbsp;Songyun Ouyang,&nbsp;Liping Dai","doi":"10.1038/s41416-026-03576-x","DOIUrl":"10.1038/s41416-026-03576-x","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 7","pages":"1179-1180"},"PeriodicalIF":7.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03576-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873141","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":"Correction: Identifying health conditions associated with an increased risk of pancreatic ductal adenocarcinoma at medium term in nationwide electronic health records of primary care physicians","authors":"Elie Rassy,&nbsp;Suzette Delaloge,&nbsp;Yannis Slaouti,&nbsp;Thomas Pudlarz,&nbsp;Béranger Lekens,&nbsp;Alice Boilève,&nbsp;Stefan Michiels,&nbsp;Maryam Karimi","doi":"10.1038/s41416-026-03597-6","DOIUrl":"10.1038/s41416-026-03597-6","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 7","pages":"1178-1178"},"PeriodicalIF":7.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03597-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863651","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":"ATR inhibitors synergise with mitomycin C to enhance cytotoxicity in patient-derived non-muscle invasive bladder cancer organoids.","authors":"Alba Zuidema, Levi Nijland, Kyah van Megesen, Mette Marit Vosjan, Bastiaan J Viergever, Onno Kranenburg, Richard P Meijer","doi":"10.1038/s41416-026-03581-0","DOIUrl":"https://doi.org/10.1038/s41416-026-03581-0","url":null,"abstract":"<p><strong>Background: </strong>There is a high recurrence rate in non-muscle invasive bladder cancer (NMIBC) patients treated with intravesical chemotherapy or BCG, indicating the need for novel treatment options. Synergy between DNA damage response inhibitors and chemotherapy has been shown for different solid tumours. Here, we explore whether combining chemotherapeutic agents with Ataxia telangiectasia and Rad3-related (ATR) kinase inhibitors is a suitable strategy to reduce recurrence in NMIBC.</p><p><strong>Methods: </strong>NMIBC patient-derived organoids (PDOs; n = 6) were exposed to mitomycin C (MMC) for 2 h, to mimic intravesical instillation, and subsequently to ATR inhibitors (berzosertib, ceralasertib, tuvusertib) for 72 h. Additionally, combination treatments with gemcitabine/epirubicin were analysed (n = 1 PDO). Cell viability and PDO regrowth potential were determined by microscopy and CellTiter-Glo luminescence assays 6 weeks post-treatment.</p><p><strong>Results: </strong>PDO viability was severely impaired after combination treatment with chemotherapy and ATR inhibitors. This effect was maintained for 6 weeks after drug exposure. In contrast, PDOs treated with only chemotherapy or ATR inhibitors showed similar proliferation rates as untreated controls in week 6.</p><p><strong>Conclusions: </strong>This study demonstrates synergy between ATR inhibitors and chemotherapy in NMIBC PDOs. Combining intravesical chemotherapy instillations with DNA damage response inhibitors should be further evaluated as a promising strategy to reduce recurrence rates for NMIBC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863640","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":"Prospective validation of a urine-based proteomics test for predicting clinically significant prostate cancer in biopsy-naïve patients.","authors":"Ana C Morillo, Kirubel Nigusu Jobre, Guillermo Lendinez Cano, Ana Blanca-Pedregosa, Daniel Lopez Ruiz, Jose Parada, Isabel Heidegger, Zoran Culig, Antonio Lopez-Beltran, Julia Carrasco-Valiente, Harald Mischak, Rafael A Medina, Juan P Campos Hernandez, Maria Frantzi, Enrique Gómez Gómez","doi":"10.1038/s41416-026-03602-y","DOIUrl":"https://doi.org/10.1038/s41416-026-03602-y","url":null,"abstract":"<p><strong>Background and objective: </strong>Prostate cancer (PCa) remains a major health burden, while existing diagnostic approaches are limited by overdiagnosis that leads to unnecessary biopsies, and by underdetection of clinically significant disease (csPCa). This study aims to prospectively validate a urine-based 19-biomarker model (19-BM) using capillary electrophoresis-mass spectrometry (CE-MS) for predicting csPCa in patients at risk.</p><p><strong>Methods: </strong>One hundred sixty-one biopsy-naïve patients at risk for csPCa underwent pre-biopsy CE-MS analysis in urine, multiparametric magnetic resonance imaging (mpMRI), and biopsy at two major hospitals. The 19-BM performance was assessed in comparison with Prostate-Specific Antigen (PSA), the European Randomised Study of Screening for Prostate Cancer (ERSPC), and mpMRI. Performance metrics included Area Under the ROC Curve (AUC), sensitivity, specificity, negative, and positive predictive values. One hundred patients receiving radical prostatectomy were evaluated to investigate the correlation of the 19-BM scores with the prostatectomy pathology.</p><p><strong>Key findings and limitations: </strong>The 19-BM scores achieved an AUC of 0.79, outperforming PSA (AUC 0.54, p < 0.0001), ERSPC (AUC 0.63, p = 0.0108), PSAD (AUC 0.61, p = 0.0021) and mpMRI (AUC 0.65, p = 0.0069). In patients with low Prostate Imaging Reporting and Data System scores (PI-RADS), 19-BM showed a sensitivity of 75% and specificity of 90%. Prospective validation of a previous nomogram combining 19-BM with mpMRI yielded an AUC of 0.82 (with specificity of 90%, sensitivity 64%).</p><p><strong>Conclusions: </strong>After prospective validation, the 19-BM demonstrates robust performance in predicting csPCa. The urine-based 19BM can serve as a valuable complement to current diagnostic methods, potentially reducing the need for unnecessary invasive procedures, also when combined with mpMRI.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148856878","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":"On-treatment core needle biopsy identifies early responders for axillary surgery de-escalation: results from a prospective cohort.","authors":"Yifan Xie, Siyu Wu, Yan Huang, Ying Zhang, Miao Mo, Yajia Gu, Zhimin Shao, Guangyu Liu","doi":"10.1038/s41416-026-03583-y","DOIUrl":"https://doi.org/10.1038/s41416-026-03583-y","url":null,"abstract":"<p><strong>Background: </strong>Increasing axillary pathologic complete response (pCR) rates after neoadjuvant chemotherapy (NACT) challenge the need for routine axillary surgery. On-treatment core needle biopsy (CNB) can assess early response, but its predictive and prognostic value for axillary surgery de-escalation remains unclear.</p><p><strong>Methods: </strong>This prospective cohort included breast cancer patients receiving on-treatment CNB (after 2-4 cycles) of the primary tumor during NACT (2013-2021). Early responders were defined as having no residual disease of on-treatment CNB. These results were compared with axillary pCR and survival outcomes.</p><p><strong>Results: </strong>The overall axillary pCR rate of 1693 patients was 54.3%. Of 500 early responders, 83.4% achieved axillary pCR. In clinically node-negative (cN0) patients, 98.0% (99/101) of those early responders presented with no nodal disease. While 79.7% of cN+ early responders achieved axillary pCR, this rate increased to 89.6% when combined with post-treatment MRI complete response (92.6% in cN1 and 90.0% in cN2 patients). Survival analysis revealed early responders with superior five-year overall and event-free survival with HR-negative tumors (p < 0.001).</p><p><strong>Conclusions: </strong>On-treatment CNB reliably identifies patients likely to achieve axillary pCR, offering an approach to guide de-escalation strategies and potentially identifying patients who may benefit from tailored systemic and surgical treatments.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838940","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}