British Journal of Cancer最新文献_第2页

A phase 1b, multicentre, dose escalation, safety and pharmacokinetics study of tilvestamab (BGB149) in relapsed, platinum-resistant, high-grade serous ovarian cancer (PROC) patients. tilvestamab （BGB149）用于复发、铂耐药、高级别浆液性卵巢癌（PROC）患者的1b期、多中心、剂量递增、安全性和药代动力学研究

IF 6.4 1区医学

British Journal of Cancer Pub Date : 2025-07-22 DOI: 10.1038/s41416-025-03090-6

Kenneth Sooi, Tuan Zea Tan, Jae-Weon Kim, Jung Yun Lee, Byoung-Gie Kim, David Micklem, Akil Jackson, David J Pinato, Charlie Gourley, Rebecca Kristeleit, Sarah P Blagden, Line Bjorge, David Shao Peng Tan

{"title":"A phase 1b, multicentre, dose escalation, safety and pharmacokinetics study of tilvestamab (BGB149) in relapsed, platinum-resistant, high-grade serous ovarian cancer (PROC) patients.","authors":"Kenneth Sooi, Tuan Zea Tan, Jae-Weon Kim, Jung Yun Lee, Byoung-Gie Kim, David Micklem, Akil Jackson, David J Pinato, Charlie Gourley, Rebecca Kristeleit, Sarah P Blagden, Line Bjorge, David Shao Peng Tan","doi":"10.1038/s41416-025-03090-6","DOIUrl":"https://doi.org/10.1038/s41416-025-03090-6","url":null,"abstract":"Background: Tilvestamab is a highly selective humanised immunoglobulin G1 anti-AXL monoclonal antibody. This phase 1 study evaluated its optimal dose, safety, tolerability, immunogenicity and pharmacokinetics (PK) in relapsed platinum-resistant HGSOC patients.Methods: Patients received tilvestamab in three dose levels (1 mg/kg, 3 mg/kg and 5 mg/kg) via IV infusion every 2 weeks. Primary objectives included safety, tolerability and PK. Exploratory objectives included overall response, progression-free survival (PFS) and quality-of-life measures. Pharmacodynamic included AXL expression, gene and protein changes by transcriptomic and proteomic analysis.Results: Between 25 February 2021 and 4 February 2022, 16 patients were enroled across 8 sites in Singapore, Korea, United Kingdom, and Norway. Median treatment duration was 6.1 weeks. Grade 3 or higher treatment-emergent adverse events occurred in 62.5% patients, but none were tilvestamab-related. Common events included fatigue (38%), anorexia (38%) infections (31%), anaemia (25%) and dyspnoea (25%). No objective responses were observed, but 7 (44%) had stable disease at 6 weeks. PK showed dose-proportional exposure and steady-state by the second dose. Pharmacodynamic analyses revealed reduced fibrosis-related gene signatures and AXL protein expression. Epithelial-mesenchymal transition reversal was seen in 2 patients.Conclusion: Tilvestamab was well-tolerated and further studies to examine the efficacy of AXL inhibition in other indications are required.Clinical trial registration: This trial is registered at https://clinicaltrials.gov .Registration number: NCT04893551. EudraCT Number: 2020-001382-36.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688975","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

Association between low-dose aspirin use and breast cancer recurrence: a Danish nationwide cohort study with up to 23 years of follow-up. 低剂量阿司匹林使用与乳腺癌复发之间的关系：一项丹麦全国队列研究，随访长达23年。

IF 6.4 1区医学

British Journal of Cancer Pub Date : 2025-07-22 DOI: 10.1038/s41416-025-03112-3

Elisabeth Solmunde, Rikke N Pedersen, Mette Nørgaard, Lene Mellemkjær, Søren Friis, Bent Ejlertsen, Thomas P Ahern, Deirdre P Cronin-Fenton

{"title":"Association between low-dose aspirin use and breast cancer recurrence: a Danish nationwide cohort study with up to 23 years of follow-up.","authors":"Elisabeth Solmunde, Rikke N Pedersen, Mette Nørgaard, Lene Mellemkjær, Søren Friis, Bent Ejlertsen, Thomas P Ahern, Deirdre P Cronin-Fenton","doi":"10.1038/s41416-025-03112-3","DOIUrl":"https://doi.org/10.1038/s41416-025-03112-3","url":null,"abstract":"Background: The anti-cancer potential of low-dose aspirin in long-term breast cancer (BC) survivors remain unknown. We evaluated the association between low-dose aspirin use and BC recurrence and mortality.Methods: Women ≥40 years diagnosed with stage I-III BC (1996-2004) were identified from the Danish Breast Cancer Group (DBCG) database and information on aspirin use from the Danish Prescription Registry. We ascertained recurrences from DBCG and via a validated algorithm. We plotted cumulative incidences of recurrence and mortality, accounting for competing risks. Using Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CI), employing landmark analyses at 5-, 10-, and 15-year post-diagnosis.Results: Among 20,509 BC survivors, 4527 developed recurrence over 232,441 person-years of follow-up. The 20-year cumulative incidence of recurrence was lower in users (17.8%) than nonusers (22.4%), with similar trends among 10-year disease-free survivors (9.9% vs. 12.7%). We observed reduced HRs of recurrence (adjusted HR5-year = 0.80, (95% CI = 0.66-0.98); HR10-year = 0.87 (0.73-1.05); HR15-year = 0.82 (0.57-1.17) in aspirin users, but increased HRs of all-cause mortality (HR5-year = 1.08 (0.96-1.21); HR10-year = 1.09 (0.96-1.24); HR15-year = 1.09 (0.80-1.31).Conclusions: The reduced recurrence risk in aspirin users may indicate potential anti-cancer effects of aspirin, though the increased risk of death suggests influence by confounding by indication and competing risks.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681995","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

Application of an obstetric comorbidity index to predict childhood cancer risk: a population based case-control study in Denmark. 应用产科合并症指数预测儿童癌症风险：丹麦一项基于人群的病例对照研究。

IF 6.4 1区医学

British Journal of Cancer Pub Date : 2025-07-21 DOI: 10.1038/s41416-025-03120-3

Cheng Yin, Tobiloba Adanma Adenekan, Chuanjie Deng, Johnni Hansen, Chisom N Iwundu, Julia E Heck

{"title":"Application of an obstetric comorbidity index to predict childhood cancer risk: a population based case-control study in Denmark.","authors":"Cheng Yin, Tobiloba Adanma Adenekan, Chuanjie Deng, Johnni Hansen, Chisom N Iwundu, Julia E Heck","doi":"10.1038/s41416-025-03120-3","DOIUrl":"https://doi.org/10.1038/s41416-025-03120-3","url":null,"abstract":"Background: Maternal health during pregnancy appears to impact childhood cancer risk, yet comprehensive studies remain scarce. This study investigates associations between childhood cancer and multiple maternal comorbidities.Methods: A population-based case-control study was conducted using Danish national registers, with maternal health conditions identified from the National Patient Register and Medical Births Registry. We employed the Obstetric Comorbidity Index using ICD-8 and ICD-10 codes. The study population (1977-2013) included 6419 cases and 160484 matched controls. Conditional logistic regression estimated pediatric cancer risk.Results: A maternal comorbidity score of one or more was linked to acute lymphocytic leukemia (ALL; OR = 1.07, 95%CI: 1.03-1.12), retinoblastoma (OR = 1.08, 95%CI: 0.94-1.23), and rhabdomyosarcoma (OR = 1.11, 95%CI: 0.98-1.26). Pre-existing diabetes (OR = 1.82, 95%CI: 1.28-2.59), previous cesarean delivery (OR = 1.20, 95%CI: 1.02-1.41), and gestational hypertension (OR = 1.27, 95%CI: 1.01-1.59) were associated with increased cancer risks in offspring. Slightly higher risks were noted for non-Hodgkin lymphoma (OR = 1.05, 95%CI: 0.96-1.16) and Burkitt lymphoma (OR = 1.08, 95%CI: 0.92-1.27) among children whose mothers had one or more comorbidities.Conclusion: An obstetric comorbidity index can predict childhood cancer risk. This highlights the need for targeted interventions to reduce adverse health consequences for offspring.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681994","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: YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways. 更正：YY1靶向微管蛋白聚合促进蛋白，通过p38/MAPK和PI3K/AKT途径抑制胰腺癌的迁移、侵袭和血管生成。

IF 6.4 1区医学

British Journal of Cancer Pub Date : 2025-07-18 DOI: 10.1038/s41416-025-03061-x

Qun Chen, Chuang Yang, Lei Chen, Jing-Jing Zhang, Wan-Li Ge, Hao Yuan, Ling-Dong Meng, Xu-Min Huang, Peng Shen, Yi Miao, Kui-Rong Jiang

引用次数: 0

Targeting gut microbiota and arginase boosts MEK inhibitors' enhancement of antitumour immunity via MHC-I upregulation in colorectal cancer. 以肠道微生物群和精氨酸酶为靶点，通过上调结肠直肠癌的MHC-I，促进MEK抑制剂增强抗肿瘤免疫。

IF 6.4 1区医学

British Journal of Cancer Pub Date : 2025-07-17 DOI: 10.1038/s41416-025-03106-1

Jingdan Zhang, Haiyan Dong, Liumei Liang, Limei Hu, Junxiong Chen, Weiqian Li, Jiaqi Liu, Yixi Su, Mengchen Shi, Yanchun Feng, Emile Z Naccasha, Cara Lewis, Huanliang Liu, Xiangling Yang, Chuangyu Wen

{"title":"Targeting gut microbiota and arginase boosts MEK inhibitors' enhancement of antitumour immunity via MHC-I upregulation in colorectal cancer.","authors":"Jingdan Zhang, Haiyan Dong, Liumei Liang, Limei Hu, Junxiong Chen, Weiqian Li, Jiaqi Liu, Yixi Su, Mengchen Shi, Yanchun Feng, Emile Z Naccasha, Cara Lewis, Huanliang Liu, Xiangling Yang, Chuangyu Wen","doi":"10.1038/s41416-025-03106-1","DOIUrl":"https://doi.org/10.1038/s41416-025-03106-1","url":null,"abstract":"Background: Elevating major histocompatibility complex class I (MHC-I) levels in tumour cells can boost antitumour immunity and enhance immunotherapy for colorectal cancer (CRC). Screening an FDA-approved drug library showed that MEK inhibitors (MEKis) significantly increase MHC-I expression in CRC cells, though the mechanisms and antitumour effects of MEKis, as well as their impact on gut microbiota, remain unclear.Methods: Dual-luciferase reporter system was employed to screen MHC-I inducers. MHC-I expression was analysed using qRT-PCR, flow cytometry, and western blot. OT-I TCR transgenic mice, subcutaneous mouse tumour models, RNA-seq, and ChIP-qPCR were used to identify the underlying mechanism. Gut microbiota was depleted using antibiotics cocktail and analysed via Shotgun sequencing, 16S rRNA sequencing and nontargeted metabolomic sequencing.Results: MEKis, particularly cobimetinib, increased MHC-I expression by inhibiting PRMT5-mediated repression of NLRC5, boosting CD8+ T cell-mediated immunity and enhancing PD-L1 blockade efficacy. Cobimetinib also altered gut microbiota, reducing L-arginine via arginase production, which compromised antitumour immunity. Arginase inhibition or L-arginine supplementation restored immune responses.Conclusions: This study uncovers a novel mechanism of MEKi-induced MHC-I expression and highlights the interplay between gut microbiota and antitumour immunity, providing insights for MEKi-based CRC immunotherapy.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658501","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

Adapting the BOADICEA breast and ovarian cancer risk models for the ethnically diverse UK population. 调整BOADICEA乳腺癌和卵巢癌风险模型以适应不同种族的英国人口。

IF 6.4 1区医学

British Journal of Cancer Pub Date : 2025-07-17 DOI: 10.1038/s41416-025-03117-y

Lorenzo Ficorella, Xin Yang, Nasim Mavaddat, Tim Carver, Hend Hassan, Joe Dennis, Jonathan Tyrer, Weang-Kee Ho, Soo-Hwang Teo, Mikael Hartman, Jingmei Li, Mikael Eriksson, Kamila Czene, Per Hall, Tameera Rahman, Andrew Bacon, Steven Hardy, Adam E Stokes, Francisca Stutzin Donoso, Stephanie Archer, Jacques Simard, Paul D P Pharoah, Juliet A Usher-Smith, Marc Tischkowitz, Douglas F Easton, Antonis C Antoniou

{"title":"Adapting the BOADICEA breast and ovarian cancer risk models for the ethnically diverse UK population.","authors":"Lorenzo Ficorella, Xin Yang, Nasim Mavaddat, Tim Carver, Hend Hassan, Joe Dennis, Jonathan Tyrer, Weang-Kee Ho, Soo-Hwang Teo, Mikael Hartman, Jingmei Li, Mikael Eriksson, Kamila Czene, Per Hall, Tameera Rahman, Andrew Bacon, Steven Hardy, Adam E Stokes, Francisca Stutzin Donoso, Stephanie Archer, Jacques Simard, Paul D P Pharoah, Juliet A Usher-Smith, Marc Tischkowitz, Douglas F Easton, Antonis C Antoniou","doi":"10.1038/s41416-025-03117-y","DOIUrl":"https://doi.org/10.1038/s41416-025-03117-y","url":null,"abstract":"Background: BOADICEA is a widely used algorithm for predicting breast and ovarian cancer risks, using a combination of genetic and lifestyle, hormonal and reproductive risk factors. However, it has largely been developed using data from White/European individuals, limiting its applicability to other ethnicities. Here, we updated BOADICEA to provide ethnicity-specific risk estimates.Methods: We utilised data from multiple sources to derive estimates for the distributions and effect sizes of risk factors in major UK ethnic groups (White, Black, South Asian, East Asian, and Mixed), along with ethnicity-specific population cancer incidences. We also developed a method for deriving adjusted polygenic scores for individuals of mixed genetic ancestry.Results: The predicted average absolute risks were smaller in all non-White ethnic groups than in Whites, and the risk distributions were narrower. The proportion of women classified as at moderate or high risk of breast or ovarian cancer, according to national guidelines, was considerably smaller in non-Whites.Discussion: The updated BOADICEA, available in the CanRisk tool ( www.canrisk.org ), is based on more appropriate estimates for non-White women in the UK. Further validation of the model in prospective studies is required. Considering these findings, risk classification guidelines for non-White women may need to be revised.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658500","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

Radiotherapy combined with anlotinib in locoregional recurrent esophageal squamous cell carcinoma after radical surgery: a prospective, Phase II clinical trial. 放疗联合安洛替尼治疗食管癌根治术后局部复发：一项前瞻性II期临床试验

IF 6.4 1区医学

British Journal of Cancer Pub Date : 2025-07-16 DOI: 10.1038/s41416-025-03101-6

Chengcheng Fan, Fang Liu, Chunyu He, Jinsong Liu, Yue Jiang, Jingwei Zhang, Xiaoyuan Wu, Yanan Sun, Xiaoli Zheng, Hongbo Wu, Hong Ge

{"title":"Radiotherapy combined with anlotinib in locoregional recurrent esophageal squamous cell carcinoma after radical surgery: a prospective, Phase II clinical trial.","authors":"Chengcheng Fan, Fang Liu, Chunyu He, Jinsong Liu, Yue Jiang, Jingwei Zhang, Xiaoyuan Wu, Yanan Sun, Xiaoli Zheng, Hongbo Wu, Hong Ge","doi":"10.1038/s41416-025-03101-6","DOIUrl":"https://doi.org/10.1038/s41416-025-03101-6","url":null,"abstract":"Background: Chemoradiotherapy is less tolerable for postoperative locoregional recurrent esophageal squamous cell carcinoma (ESCC).Methods: ESCC patients with three or fewer locoregional recurrent lesions after radical surgery were enrolled. Anlotinib (12 mg, d1-14) was administered with radiotherapy (50.4-59.4 Gy) concurrently for two cycles, followed by sequentially for another two cycles. The primary endpoints were objective response rate (ORR) and toxicity.Results: Between October 2019 and July 2022, 40 patients were eligible. The ORR was 90.0% (20.0% complete response, 70.0% partial response). The median local failure-free survival, distant metastasis-free survival, progression-free survival, and overall survival were 21.7 (95% CI, 7.839-35.627), 26.4 (95% CI, 17.706-35.028), 12.7 (95% CI, 4.023-21.377), and 29.9 months (95% CI, 18.543-41.323), respectively. Grade 3 adverse events occurred in only two patients (5.0%) who developed hypertension. No grade 4 treatment-related adverse events were observed.Conclusions: The regimen of radiotherapy combined with anlotinib demonstrated high efficacy with tolerable toxicity in postoperative locoregional recurrent ESCC. This novel regimen provided a selectable treatment strategy for such patients, especially for those who cannot tolerate or refuse chemotherapy. Further randomised controlled trials are warranted.Clinical trial registration: Chinese Clinical Trial Registry (ChiCTR1900025752).","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648610","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

Single-cell spatial analysis with Xenium reveals anti-tumour responses of CXCL13 + T and CXCL9+ cells after radiotherapy combined with anti-PD-L1 therapy. Xenium单细胞空间分析揭示了CXCL13 + T和CXCL9+细胞在放疗联合抗pd - l1治疗后的抗肿瘤反应。

IF 6.4 1区医学

British Journal of Cancer Pub Date : 2025-07-16 DOI: 10.1038/s41416-025-03088-0

Shunsuke A Sakai, Hidekazu Oyoshi, Masaki Nakamura, Tetsuro Taki, Kotaro Nomura, Hidehiro Hojo, Hidenari Hirata, Atsushi Motegi, Yuka Nakamura, Junko Zenkoh, Keiju Aokage, Akira Hamada, Motohiro Kojima, Takeshi Kuwata, Katsuya Tsuchihara, Tetsuo Akimoto, Junichi Soh, Tetsuya Mitsudomi, Masahiro Tsuboi, Genichiro Ishii, Yutaka Suzuki, Ayako Suzuki, Riu Yamashita, Shun-Ichiro Kageyama

{"title":"Single-cell spatial analysis with Xenium reveals anti-tumour responses of CXCL13 + T and CXCL9+ cells after radiotherapy combined with anti-PD-L1 therapy.","authors":"Shunsuke A Sakai, Hidekazu Oyoshi, Masaki Nakamura, Tetsuro Taki, Kotaro Nomura, Hidehiro Hojo, Hidenari Hirata, Atsushi Motegi, Yuka Nakamura, Junko Zenkoh, Keiju Aokage, Akira Hamada, Motohiro Kojima, Takeshi Kuwata, Katsuya Tsuchihara, Tetsuo Akimoto, Junichi Soh, Tetsuya Mitsudomi, Masahiro Tsuboi, Genichiro Ishii, Yutaka Suzuki, Ayako Suzuki, Riu Yamashita, Shun-Ichiro Kageyama","doi":"10.1038/s41416-025-03088-0","DOIUrl":"https://doi.org/10.1038/s41416-025-03088-0","url":null,"abstract":"Background: The standard treatment for unresectable non-small cell lung cancer (NSCLC) is anti-PD-L1 therapy combined with chemoradiotherapy (anti-PD-L1-CRT). Although some patients achieve complete cancer eradication and cure, more than half of patients retain persistent cancer cells. Our research aimed to unravel the nuanced mechanisms involved in both immune attack and evasion induced by anti-PD-L1-CRT with single cell spatial transcriptome.Methods: Xenium is a cutting-edge single-cell spatial analysis tool that enables pathology-based and single-cell analyses while preserving spatial information. In our study, we used Xenium to identify the tumour microenvironment (TME), immune dynamics, and residual cancer cells at the single-cell level following treatment with anti-PD-L1-CRT.Results: Posttreatment alterations included a significant increase in CXCL9+ cells and CXCL13 + T cells, particularly around tumour cells. Additionally, we discovered that CXCL13 + T cells directly impact cancer cells in the posttreatment environment. Moreover, we identified clusters of immune-cold cancer cells posttreatment, revealing their activation of DNA repair pathways and high proliferative capacity. The novel spatial analysis tool Xenium enabled identification of the immune environment at the single-cell level following treatment with anti-PD-L1-CRT, elucidating its characteristics.Conclusions: These findings suggest potential advancements in developing new treatments to improve posttreatment immune responses and address resistance challenges.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648611","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

Novel mutations of SRPX facilitate the stemness and malignant progression of glioma. SRPX的新突变促进胶质瘤的发生和恶性进展。

IF 6.4 1区医学

British Journal of Cancer Pub Date : 2025-07-15 DOI: 10.1038/s41416-025-03091-5

Siyuan Tang, Chunhui Qu, Mingyu Zhang, Peijun Zhou, Xingzhi Peng, Zhuan Zhou, Liangfang Shen, Lifang Yang

{"title":"Novel mutations of SRPX facilitate the stemness and malignant progression of glioma.","authors":"Siyuan Tang, Chunhui Qu, Mingyu Zhang, Peijun Zhou, Xingzhi Peng, Zhuan Zhou, Liangfang Shen, Lifang Yang","doi":"10.1038/s41416-025-03091-5","DOIUrl":"https://doi.org/10.1038/s41416-025-03091-5","url":null,"abstract":"Background: Explorations of genomic profiles are of great clinical significance for glioma due to the high tumor heterogeneity and stemness. High-depth sequencing enabled to identify driver genes and potential treatment targets in glioma.Methods: A whole exome sequencing analysis of 27 Chinese patients was conducted and somatic mutation signatures were analyzed using validated computational methods. The biological roles of SRPX mutations and subsequent regulatory mechanisms were revealed by common experimental methods.Results: We intriguingly found that SRPX drove glioma progression with two frequent in-frame deletion mutations of p.L14DEL and p.L23DEL. Mechanistically, both the two mutations of SRPX promoted binding with transcription factor AHR on its promoter, upregulated gene transcription of itself, then activated EGFR/ Akt/ Nestin pathway and contributed to aggressive tumor phenotypes and animal tumor growth. Further, knockdown of AHR or application of Akt inhibitor suppressed the oncogenic role of mutated SRPX.Conclusions: Our study highlighted the landscape of glioma in revealing a non-distinctive mutation and signaling pathway profile between low and high grades. More importantly, we identified a novel role of SRPX mutations in acceleration to stemness and malignant progression, which could provide new targets in improving outcomes of glioma.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641790","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

High expression of the cachexia-related protein Fn14 in esophageal squamous cell carcinoma correlates with poor chemotherapy response and anti-Fn14 therapy decreases chemotherapeutic resistance. 恶病质相关蛋白Fn14在食管鳞状细胞癌中的高表达与化疗反应差相关，抗Fn14治疗可降低化疗耐药。

IF 6.4 1区医学

British Journal of Cancer Pub Date : 2025-07-15 DOI: 10.1038/s41416-025-03087-1

Kei Adachi, Kotaro Yamashita, Yu Kamakura, Kota Momose, Takuro Saito, Koji Tanaka, Tomoki Makino, Kazuyoshi Yamamoto, Tsuyoshi Takahashi, Yukinori Kurokawa, Kiyokazu Nakajima, Hidetoshi Eguchi, Yuichiro Doki

{"title":"High expression of the cachexia-related protein Fn14 in esophageal squamous cell carcinoma correlates with poor chemotherapy response and anti-Fn14 therapy decreases chemotherapeutic resistance.","authors":"Kei Adachi, Kotaro Yamashita, Yu Kamakura, Kota Momose, Takuro Saito, Koji Tanaka, Tomoki Makino, Kazuyoshi Yamamoto, Tsuyoshi Takahashi, Yukinori Kurokawa, Kiyokazu Nakajima, Hidetoshi Eguchi, Yuichiro Doki","doi":"10.1038/s41416-025-03087-1","DOIUrl":"https://doi.org/10.1038/s41416-025-03087-1","url":null,"abstract":"Background: In cancer cachexia, cytokine release by tumours causes weight loss, decreased therapeutic efficacy, and worsened prognosis. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and fibroblast inducible factor 14 (Fn14) are cancer cachexia-related proteins; however, their expression in oesophageal squamous cell carcinoma (ESCC) and association with therapeutic resistance remain unclear.Methods: We evaluated how Fn14 knockdown and overexpression in ESCC lines (TE6 and TE10) contributed to proliferation, migration, and chemotherapy resistance in vitro and in vivo. In 135 ESCC patients who underwent esophagectomy after neoadjuvant chemotherapy, tumour expression of TWEAK and Fn14 was evaluated immunohistochemically to assess the association with clinicopathological factors and prognosis, including chemotherapeutic efficacy.Results: Proliferation, migration, and chemotherapy resistance of ESCC cell lines were decreased by Fn14 knockdown but increased by Fn14 overexpression. Patients with Fn14-overexpressing ESCC had a decreased response rate to neoadjuvant chemotherapy and significantly lower rates of overall and recurrence-free survival, while concurrent expression of TWEAK and Fn14 was associated with further reductions in the response rate to chemotherapy and the rates of overall and recurrence-free survival.Conclusions: TWEAK and Fn14 expression was associated with treatment resistance and prognosis in ESCC. Inhibiting the TWEAK/Fn14 axis may reduce treatment resistance and improve prognosis.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641861","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