British Journal of Cancer最新文献

Modeling response to the KRAS-G12C inhibitor AZD4625 in KRAS^G12C NSCLC patient-derived xenografts reveals insights into primary resistance mechanisms. KRASG12C非小细胞肺癌患者来源的异种移植物对KRASG12C抑制剂AZD4625的反应建模揭示了原发性耐药机制的见解。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-10-11 DOI: 10.1038/s41416-025-03216-w

Joshua C Rosen, Pinjiang Cao, Nhu-An Pham, Matthew Waas, Quan Li, Katrina Hueniken, Mutian Wang, Roya Navab, Leanne Wybenga-Groot, Nikolina Radulovich, Michael Niedbala, Alex Koers, Sarah Ross, Michael F Moran, Adrian Sacher, Ming-Sound Tsao

{"title":"Modeling response to the KRAS-G12C inhibitor AZD4625 in KRASG12C NSCLC patient-derived xenografts reveals insights into primary resistance mechanisms.","authors":"Joshua C Rosen, Pinjiang Cao, Nhu-An Pham, Matthew Waas, Quan Li, Katrina Hueniken, Mutian Wang, Roya Navab, Leanne Wybenga-Groot, Nikolina Radulovich, Michael Niedbala, Alex Koers, Sarah Ross, Michael F Moran, Adrian Sacher, Ming-Sound Tsao","doi":"10.1038/s41416-025-03216-w","DOIUrl":"https://doi.org/10.1038/s41416-025-03216-w","url":null,"abstract":"Background: KRASG12C alterations are present in ~13% of lung adenocarcinomas. AZD4625 is a covalent small molecule inhibitor that selectively binds and inhibits GDP-KRASG12C, leading to reduced cell viability and protein signaling responsible for tumor survival in models with this gain-of-function alteration.Methods: We studied short-term changes in signaling and mechanisms of primary resistance to AZD4625 in twelve KRASG12C lung adenocarcinoma patient-derived xenografts (PDX) and six organoids derived from these twelve models.Results: Sustained tumor regression in four (33%) PDXs was observed while the remaining eight models were intrinsically resistant to AZD4625. Organoid responses to AZD4625 were concordant with their derived PDXs. Acute AZD4625 exposure significantly decreased gene expression of the ERK1/2 negative regulator, DUSP6, in all models while protein MAPK and AKT/mTOR signals were downregulated more frequently in the AZD4625-sensitive than AZD4625-resistant cohorts. Analyzing PDX transcriptomes and proteomes identified mTOR signaling as a putative mechanism of primary resistance to AZD4625.Conclusions: Our findings confirm AZD4625 as a highly active KRASG12C inhibitor. This data also supports the use of PDX models in understanding resistance mechanisms that may be leveraged to develop more active combination therapies.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circulating tumor DNA from blood and cerebrospinal fluid in DLBCL: simultaneous evaluation of mutations, IG rearrangement, and IG clonality. DLBCL患者血液和脑脊液循环肿瘤DNA：突变、IG重排和IG克隆的同时评估

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-10-09 DOI: 10.1038/s41416-025-03217-9

Han Zhang, Lingfeng Liu, Xiaohui Zhang, Ping Chen, Xingping Lang, Jingjing Feng, Yiting Wang, Yufei Xie, Shouli Wang, Sheng Xiao, Bingzong Li

{"title":"Circulating tumor DNA from blood and cerebrospinal fluid in DLBCL: simultaneous evaluation of mutations, IG rearrangement, and IG clonality.","authors":"Han Zhang, Lingfeng Liu, Xiaohui Zhang, Ping Chen, Xingping Lang, Jingjing Feng, Yiting Wang, Yufei Xie, Shouli Wang, Sheng Xiao, Bingzong Li","doi":"10.1038/s41416-025-03217-9","DOIUrl":"https://doi.org/10.1038/s41416-025-03217-9","url":null,"abstract":"Background: Circulating tumor DNA (ctDNA) is a promising biomarker for monitoring minimal residual disease (MRD), assessing disease status, and guiding treatment in diffuse large B-cell lymphoma (DLBCL). Current ctDNA assays rarely detect immunoglobulin (IG) fusions. This study evaluates a novel assay that simultaneously detects mutations, IG fusions, and IG V(D)J clonality in plasma and cerebrospinal fluid (CSF) to enhance molecular profiling and CNS monitoring.Methods: A prospective analysis was conducted in 57 DLBCL patients. Genomic alterations in plasma and CSF ctDNA were compared to those in tumor tissue using targeted next-generation sequencing (NGS).Results: Mutations, IG fusions, and IG V(D)J clonality were detected in 100%, 72.2%, and 78.6% of plasma ctDNA samples, respectively. Plasma ctDNA also revealed additional mutations absent in tumor tissue, reflecting clonal heterogeneity. The incorporation of IG fusion detection enabled molecular subtyping without requiring FISH. In CSF, ctDNA analysis identified genomic alterations in 8 cases, whereas conventional imaging and cytology confirmed CNS involvement in only 3, demonstrating the superior sensitivity of ctDNA for CNS surveillance.Conclusion: This ctDNA assay offers a non-invasive, integrated approach for genomic profiling and disease monitoring in DLBCL, with improved sensitivity for CNS detection and potential to inform personalized treatment strategies.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: Phosphorylation-dependent regulation of SPOP by LIMK2 promotes castration-resistant prostate cancer. 更正：LIMK2磷酸化依赖性调控SPOP促进去势抵抗性前列腺癌。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-10-09 DOI: 10.1038/s41416-025-03212-0

Kumar Nikhil, Hanan S Haymour, Mohini Kamra, Kavita Shah

引用次数: 0

Serum multiomics prediction of prognosis and adverse reactions to concurrent chemoradiotherapy in patients with esophageal cancer. 食管癌患者同步放化疗预后及不良反应的血清多组学预测。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-10-08 DOI: 10.1038/s41416-025-03229-5

Wen-Zhi Wu, He-Cheng Huang, Guang-Hui Zhu, Lian-Di Liao, Xu-Li Chen, Zhi-Mao Li, Man-Yu Chu, Shuai-Xia Yu, Dian Wang, En-Min Li, Li-Yan Xu

{"title":"Serum multiomics prediction of prognosis and adverse reactions to concurrent chemoradiotherapy in patients with esophageal cancer.","authors":"Wen-Zhi Wu, He-Cheng Huang, Guang-Hui Zhu, Lian-Di Liao, Xu-Li Chen, Zhi-Mao Li, Man-Yu Chu, Shuai-Xia Yu, Dian Wang, En-Min Li, Li-Yan Xu","doi":"10.1038/s41416-025-03229-5","DOIUrl":"https://doi.org/10.1038/s41416-025-03229-5","url":null,"abstract":"Objective: Concurrent chemoradiotherapy (CCRT) is an important treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). There is still a lack of reliable means to predict efficacy, prognosis and hematologic toxicity.Design: We analyzed 127 serum samples before CCRT and 93 serum samples after CCRT from 127 ESCC patients via metabolomics by GC-MS. Combined with Olink proteomics, we constructed models to predict response and survival through machine learning. Multiple linear regression was used to construct hematologic toxicity prediction models. In combination with the proteomics of ESCC, metabolic changes were studied.Results: A prediction model for the efficacy to CCRT was established via serum metabolomics and proteomics (Train, CR/nCR = 28/50, AUC = 0.9848, 95% CI = 0.9639-1.0000; Test, CR/nCR = 17/15, AUC = 0.8854, 95% CI = 0.7800-0.9908). A survival prediction model was established (n = 109, C-index = 0.7640, 95% CI = 0.7140-0.8140). Linear models for predicting hematologic toxicity were constructed (n = 111, R > 0.7). L-serine is important for the prognosis of patients with ESCC treated with CCRT, and SHMT2 is a key protein in serine metabolism that affects the efficacy of CCRT.Conclusion: The combination of serum metabolomics with proteomics can effectively predict the prognosis and hematologic toxicity, which can provide important data for patients to choose treatment methods.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The mediating role of new morbidities on social inequality in mortality after curative cancer treatment - a SEQUEL study. 新发病对治愈性癌症治疗后死亡率的社会不平等的中介作用-一项SEQUEL研究。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-10-07 DOI: 10.1038/s41416-025-03225-9

Trille Kristina Kjaer, Mia Klinten Grand, Anne Katrine Graudal Levinsen, Erik Jakobsen, Michael Borre, Robert Zachariae, Peer Christiansen, Søren Laurberg, Peter Christensen, Lisbet Rosenkrantz Hölmich, Peter de Nully Brown, Christoffer Johansen, Susanne K Kjaer, Susanne Oksbjerg Dalton

{"title":"The mediating role of new morbidities on social inequality in mortality after curative cancer treatment - a SEQUEL study.","authors":"Trille Kristina Kjaer, Mia Klinten Grand, Anne Katrine Graudal Levinsen, Erik Jakobsen, Michael Borre, Robert Zachariae, Peer Christiansen, Søren Laurberg, Peter Christensen, Lisbet Rosenkrantz Hölmich, Peter de Nully Brown, Christoffer Johansen, Susanne K Kjaer, Susanne Oksbjerg Dalton","doi":"10.1038/s41416-025-03225-9","DOIUrl":"https://doi.org/10.1038/s41416-025-03225-9","url":null,"abstract":"Background: Socioeconomic factors are linked to cancer survival. While cancer stage and treatment mediate this association, the role of new morbidities after cancer treatment is less understood. We investigated educational disparities in cancer mortality and whether it is explained by differences in death from new morbidities.Methods: 85,849 cancer survivors with lung, breast, prostate, colorectal cancers were included. Follow-up for overall and cause-specific death began one year after diagnosis, lasting up to 16 years. Cox proportional hazard models estimated the association between education and death. Mediation analyses explored whether new morbidities mediated this association.Results: Survivors with short education had higher mortality, particularly after breast and colon cancers, with a significant proportion of deaths due to new morbidities (breast cancer e.g. new primary cancers (HR 1.59, 95% CI:1.35,1.87), kidney and urinary problems (HR 4.16, 95% CI:1.24,13.97), and chronic respiratory issues (HR 2.99, 95% CI:1.86-4.79). Similar trends were observed in colon cancer survivors e.g. ischemic heart disease (HR 1.70, 95% CI:1.13,2.56) and heart failure (HR 3.53, 95% CI:1.35,9.19). Although some new morbidities were statistically significant mediators, they accounted for only a small proportion of the effects.Conclusions: Educational disparities persist in cancer survivorship, with new morbidities contributing to higher mortality rates among survivors with shorter education.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Breast cancer cell-derived adrenomedullin confers cancer-associated adipose remodeling through the cAMP/Creb1/Zeb1 axis. 乳腺癌细胞源性肾上腺髓质素通过cAMP/Creb1/Zeb1轴赋予癌症相关的脂肪重塑。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-10-06 DOI: 10.1038/s41416-025-03219-7

Xiao Chen, Lixia Cao, Mengdan Feng, Qiuying Shuai, Min Guo, Zhaoxian Li, Chunchun Qi, Jie Shi, Yuxin Liu, Siyu Zuo, Tianwen Yu, Huayu Hu, Yanjing Wang, Yao Xue, Peiqing Sun, Yi Shi, Hang Wang, Lei Liu, Shuang Yang

{"title":"Breast cancer cell-derived adrenomedullin confers cancer-associated adipose remodeling through the cAMP/Creb1/Zeb1 axis.","authors":"Xiao Chen, Lixia Cao, Mengdan Feng, Qiuying Shuai, Min Guo, Zhaoxian Li, Chunchun Qi, Jie Shi, Yuxin Liu, Siyu Zuo, Tianwen Yu, Huayu Hu, Yanjing Wang, Yao Xue, Peiqing Sun, Yi Shi, Hang Wang, Lei Liu, Shuang Yang","doi":"10.1038/s41416-025-03219-7","DOIUrl":"https://doi.org/10.1038/s41416-025-03219-7","url":null,"abstract":"Background: Breast cancer cells that break through the basement membrane interact directly with neighboring adipocytes. Therefore, adipocytes adjacent to the invasive front of tumour undergo lipolysis and transform into cancer-associated adipocytes (CAAs), which is vital for the malignant progression of breast cancer. However, tumor-derived factors that trigger this process are still to be determined.Methods: Transcriptome sequencing was used to identify the downstream transcription factor of adrenomedullin (AM). Tet-On system was used to construct the 3T3-L1 cell line with inducible overexpression of Zeb1. Adipocyte-specific knock-in Zeb1 transgenic mice (Zeb1adiTG) were used to construct an allograft tumor model.Results: Breast cancer cell-derived AM downregulated the transcriptional expression of Zeb1 by triggering the cAMP/PKA/Creb1 pathway, thereby exerting lipolytic effects in CAAs. On the contrary, adipose tissue-specific upregulation of Zeb1 significantly attenuated AM-induced lipolytic phenotypes. Of note, we used the Zeb1adiTG mice to construct allograft tumor models. The results confirmed that breast cancer cell-derived AM conferred tumorigenicity in vivo, which effect was predominantly dependent on the aberrant expression of adipocyte-specific Zeb1.Conclusions: These findings collectively suggested that breast cancer cell-derived AM promotes lipid metabolic reprogramming through a Zeb1-dependent manner in CAAs, which displays significant clinical implications and may provide promising therapeutic approaches for targeting the breast cancer-associated adipose microenvironment.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Methyl-CpG-binding domain 3 inhibits epithelial-mesenchymal transition in pancreatic cancer cells via TGF-β/Smad signalling. 更正：甲基- cpg结合结构域3通过TGF-β/Smad信号传导抑制胰腺癌细胞上皮-间质转化。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-10-06 DOI: 10.1038/s41416-025-03208-w

Min Xu, Junbo He, Jie Li, Wen Feng, Hailang Zhou, Hong Wei, Meng Zhou, Ying Lu, Jian Zeng, Wanxin Peng, Fengyi Du, Aihua Gong

引用次数: 0

Editorial Expression of Concern: Decreased levels of baseline and drug-induced tubulin polymerisation are hallmarks of resistance to taxanes in ovarian cancer cells and are associated with epithelial-to-mesenchymal transition. 关注的编辑表达：基线水平和药物诱导的微管蛋白聚合水平的降低是卵巢癌细胞对紫杉烷耐药的标志，并与上皮到间质转化有关。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-10-06 DOI: 10.1038/s41416-025-03231-x

George E Duran, Yan C Wang, François Moisan, E Brian Francisco, Branimir I Sikic

引用次数: 0

Lung cancer burden attributable to ambient particulate matter: a nationally representative population-based case-control study. 环境颗粒物所致肺癌负担：一项具有全国代表性的基于人群的病例对照研究

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-10-06 DOI: 10.1038/s41416-025-03207-x

Rawan A N Alhattab, Jennifer M McKinley, Ruth F Hunter, Claire M Delargy, Sara M Wallace, Damien Bennett, Deirdre Fitzpatrick, Helen Mitchell, Bernadette McGuinness, Angela Scott, Gareth McKay, Liacine Bouaoun, Valerie McCormack, Daniel R S Middleton

{"title":"Lung cancer burden attributable to ambient particulate matter: a nationally representative population-based case-control study.","authors":"Rawan A N Alhattab, Jennifer M McKinley, Ruth F Hunter, Claire M Delargy, Sara M Wallace, Damien Bennett, Deirdre Fitzpatrick, Helen Mitchell, Bernadette McGuinness, Angela Scott, Gareth McKay, Liacine Bouaoun, Valerie McCormack, Daniel R S Middleton","doi":"10.1038/s41416-025-03207-x","DOIUrl":"https://doi.org/10.1038/s41416-025-03207-x","url":null,"abstract":"Background: Particulate matter with a diameter of 2.5 micrometers or less (PM2.5) is a known lung carcinogen, but its impact in low-pollution settings is less understood. We assessed the association between long-term PM2.5 exposure and lung cancer risk in Northern Ireland (NI), a region with relatively low air pollution levels.Methods: We conducted a population-based case-control study using data from the Northern Ireland Cancer Registry and the Northern Ireland Cohort for the Longitudinal Study of Ageing. The study included 917 lung cancer cases diagnosed in 2014 and 8,088 controls without lung cancer. Eight-year average PM2.5 exposure was estimated by linking residential postcodes to 1 km² resolution pollution maps. Fully adjusted logistic regression models were used, controlling for key confounders including smoking status and deprivation index to estimate odds ratios (ORs) and their 95% confidence intervals (95% CI), and population attributable fractions (PAFs).Results: Individuals in the highest PM2.5 tertile (>9.6 µg/m³) had a 37% increased lung cancer risk (OR: 1.37; 95% CI: 1.12-1.68) compared to the lowest tertile (<7.4 µg/m³). The association was stronger in women (OR: 1.79; 95% CI: 1.32-2.44) and not detected in men. Exposure above 10 µg/m³ accounted for 10% of cases, approximately 137 preventable lung cancers annually.Discussion: Even in low-pollution regions, PM2.5 contributes to lung cancer risk, especially in women. Strengthened air quality measures are needed to reduce preventable disease.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: CD49a⁺ NK cells promote esophageal cancer development by inducing MDSCs infiltration via GM-CSF. 更正：CD49a+ NK细胞通过GM-CSF诱导MDSCs浸润，促进食管癌的发展。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2025-10-06 DOI: 10.1038/s41416-025-03220-0

Kele Cui, Shouxin Hu, Yanfang Zha, Keshuo Ding, Haiming Wei, Min Cheng, Xinyu Mei

引用次数: 0