British Journal of Cancer最新文献_第10页

Sarcopenia in head and neck cancer: the complexity of skeletal muscle mass cut-off values 头颈癌中的肌肉减少症：骨骼肌质量临界值的复杂性。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-23 DOI: 10.1038/s41416-026-03381-6

Hugo C. van Heusden, Remco de Bree

引用次数: 0

Alectinib boosts anti-tumor efficacy of disialoganglioside 2 chimeric antigen receptor T cells in ALK-mutated neuroblastoma by suppressing programmed death-ligand 1 Alectinib通过抑制程序性死亡配体1提高alk突变的神经母细胞瘤中二联神经节苷脂2嵌合抗原受体T细胞的抗肿瘤疗效。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-23 DOI: 10.1038/s41416-026-03363-8

Yuya Sugitatsu, Akimasa Tomida, Masaya Suematsu, Tomoya Inoue, Hiroshi Kubo, Yozo Nakazawa, Shigeki Yagyu, Tomoko Iehara

{"title":"Alectinib boosts anti-tumor efficacy of disialoganglioside 2 chimeric antigen receptor T cells in ALK-mutated neuroblastoma by suppressing programmed death-ligand 1","authors":"Yuya Sugitatsu, Akimasa Tomida, Masaya Suematsu, Tomoya Inoue, Hiroshi Kubo, Yozo Nakazawa, Shigeki Yagyu, Tomoko Iehara","doi":"10.1038/s41416-026-03363-8","DOIUrl":"10.1038/s41416-026-03363-8","url":null,"abstract":"High-risk ALK-mutant neuroblastoma (NB) presents challenges due to drug resistance and an immunosuppressive tumour microenvironment (TME). Combining molecular targeted therapy with adoptive cell therapy offers a potential therapeutic strategy. To investigate the effects of alectinib, an ALK inhibitor, with disialoganglioside 2 (GD2) chimeric antigen receptor T (CAR-T) cell therapy in overcoming immune evasion in ALK-mutant NB. Interferon gamma-induced programmed death-ligand 1 (PD-L1) expression and ALK signalling were analysed in ALK-mutant NB cells. The combination of alectinib and GD2 CAR-T cells was assessed in vitro, including sequential co-culture assays, and in vivo in an ALK-mutant xenograft model with multiple treatment arms. Alectinib suppressed PD-L1 expression by inhibiting ALK downstream pathways, including STAT3 and ERK1/2 phosphorylation. In vitro studies showed enhanced anti-tumour efficacy of GD2 CAR-T cells in combination with alectinib, with synergistic effect becoming evident in sequential coculture models. In vivo, the combination therapy reduced tumour growth, extended survival, and was associated with decreased PD-L1 expression and increased CAR-T cell infiltration. Alectinib enhances the efficacy of GD2 CAR-T therapy in ALK-mutant NB primarily by attenuating PD-L1-mediated immune evasion, supporting its potential as a combinatorial therapeutic strategy.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"134 10","pages":"1488-1496"},"PeriodicalIF":6.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497712","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

Neoadjuvant immunochemoradiotherapy with nivolumab, paclitaxel, and cisplatin followed by esophagectomy for locally advanced esophageal squamous cell carcinoma 新辅助免疫放化疗联合纳武单抗、紫杉醇和顺铂治疗局部晚期食管鳞状细胞癌，后行食管切除术。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-20 DOI: 10.1038/s41416-026-03349-6

Ta-Chen Huang, Jhe-Cyuan Guo, Chia-Chi Lin, Hung-Yang Kuo, Chien-Huai Chuang, Jason, Chia-Hsien Cheng, Feng-Ming Hsu, Jang-Ming Lee, Pei-Ming Huang, Cher-Wei Liang, Yu-I Li, Chih-Hung Hsu

{"title":"Neoadjuvant immunochemoradiotherapy with nivolumab, paclitaxel, and cisplatin followed by esophagectomy for locally advanced esophageal squamous cell carcinoma","authors":"Ta-Chen Huang, Jhe-Cyuan Guo, Chia-Chi Lin, Hung-Yang Kuo, Chien-Huai Chuang, Jason, Chia-Hsien Cheng, Feng-Ming Hsu, Jang-Ming Lee, Pei-Ming Huang, Cher-Wei Liang, Yu-I Li, Chih-Hung Hsu","doi":"10.1038/s41416-026-03349-6","DOIUrl":"10.1038/s41416-026-03349-6","url":null,"abstract":"Nivolumab is effective in treating patients with esophageal squamous cell carcinoma (ESCC). The efficacy of nivolumab in combination with neoadjuvant chemoradiotherapy (CRT) remains unclear. In this phase II trial with Simon’s 2-stage design, neoadjuvant nivolumab, paclitaxel, and cisplatin were administered with radiotherapy followed by esophagectomy to patients with locally advanced ESCC. The primary endpoint was pathological complete response (pCR). The secondary endpoints were feasibility, safety, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). A total of 17 patients were enrolled in stage I. Fourteen patients received esophagectomy, with pCR achieved in 4, below the criterion for continuing to stage II. All grade and ≥grade 3 treatment emergent adverse events (TEAEs) occurred in 15 and 4 patients, respectively. Immune-related TEAEs occurred in 7; none were ≥ grade 3. The median durations of RFS, PFS, and OS were 8, 12, and 25 months, respectively. Patients with high expression of PD-L1 had higher pCR rate (100% vs 18%, P = 0.019). Nivolumab in combination with neoadjuvant CRT is safe for patients with locally advanced ESCC, and may be beneficial in those with high PD-L1 expression. NCT05130684.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"134 10","pages":"1403-1412"},"PeriodicalIF":6.8,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03349-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490699","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}

引用次数: 0

Patient-centered outcomes according to cancer status in cardiac surgery patients: a population-based cohort study 心脏手术患者癌症状态的以患者为中心的结局：一项基于人群的队列研究

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-16 DOI: 10.1038/s41416-026-03358-5

Habib Jabagi, Joshua G. Lee, Osamu W. Yasui, Mamas A. Mamas, Louise Y. Sun

{"title":"Patient-centered outcomes according to cancer status in cardiac surgery patients: a population-based cohort study","authors":"Habib Jabagi, Joshua G. Lee, Osamu W. Yasui, Mamas A. Mamas, Louise Y. Sun","doi":"10.1038/s41416-026-03358-5","DOIUrl":"10.1038/s41416-026-03358-5","url":null,"abstract":"More cancer survivors are undergoing cardiac surgery, but their postoperative outcomes remain poorly understood. We aimed to describe the incidence and predictors of postoperative major adverse cardiovascular events (MACE) and patient-defined cardiovascular and non-cardiovascular events (PACE) by cancer status. We conducted a retrospective cohort study (2016-2022) among U.S. adults (≥18 years) undergoing cardiac surgery in MarketScan and Medicare databases. Co-primary outcomes were MACE (stroke, heart failure, myocardial infarction, repeat revascularization) and PACE (stroke, heart failure, new-onset dialysis, long-term care admission, ventilator-dependence). Cox regression evaluated the association of cancer status with postoperative outcomes. Among 61,581 patients (74.1% male; mean age 61 ± 10.9 years), 5381 (8.7%) had cancer. Although cancer patients exhibited higher unadjusted MACE and PACE over 2.0 ± 1.7 years (p < 0.001), multivariable analyses showed no significant association between cancer status and MACE or PACE at 30-days or at long-term follow-up MACE (aHR 1.05, 95%CI [0.99–1.10]) and PACE (aHR 1.02, [0.96–1.08]). Blood (aHR 1.13, [1.01–1.26]) and lung cancers (aHR 1.32, [1.08–1.62]) were associated with increased MACE risk, while digestive (aHR 1.17, [1.00–1.36]) and blood (aHR 1.14, [1.01–1.28]) cancers were linked to higher PACE risk. Factors more strongly predictive of PACE than MACE included older age, female sex and valvular/complex surgeries. Cancer status alone should not preclude cardiac surgery. A personalised, multidisciplinary approach may help optimise outcomes and better manage risks in this high-risk population.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"134 10","pages":"1447-1458"},"PeriodicalIF":6.8,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467051","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

Addition of zoledronic acid to consolidation chemotherapy in Ewing sarcoma—EURO EWING 2012 (EE2012): an international, open-label, randomised controlled phase III trial 在Ewing肉瘤的巩固化疗中加入唑来膦酸- euro Ewing 2012 (EE2012)：一项国际、开放标签、随机对照III期试验。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-15 DOI: 10.1038/s41416-026-03367-4

Brennan Bernadette, Laura Kirton, Perrine Marec-Bérard, Nathalie Gaspar, Valerie Laurence, Javier Martín-Broto, Hans Gelderblom, Cormac Owens, Jennifer Anderton, Sandra J. Strauss, Jane Wingrove, Veronica Moroz, Jeremy Whelan, Lisa L. Hjalgrim, Keith Wheatley, Piers Gaunt

{"title":"Addition of zoledronic acid to consolidation chemotherapy in Ewing sarcoma—EURO EWING 2012 (EE2012): an international, open-label, randomised controlled phase III trial","authors":"Brennan Bernadette, Laura Kirton, Perrine Marec-Bérard, Nathalie Gaspar, Valerie Laurence, Javier Martín-Broto, Hans Gelderblom, Cormac Owens, Jennifer Anderton, Sandra J. Strauss, Jane Wingrove, Veronica Moroz, Jeremy Whelan, Lisa L. Hjalgrim, Keith Wheatley, Piers Gaunt","doi":"10.1038/s41416-026-03367-4","DOIUrl":"10.1038/s41416-026-03367-4","url":null,"abstract":"Pre-clinical data demonstrated anti-tumour effect in Ewing sarcoma (ES) for zoledronic acid. This provided the rationale for the second randomisation (R2) in the EURO EWING 2012 (EE2012) trial, whether the addition of zoledronic acid to consolidation chemotherapy improved clinical outcomes. EE2012 was a European academic, open-label, randomised controlled phase III clinical trial. Patients with ES or Ewing-like sarcomas were included (R1). Patients meeting the R2 eligibility criteria (age 5–49 years) were randomised (1:1) to receive either nine cycles of zoledronic acid or no zoledronic acid with the R1 allocated consolidation chemotherapy. Primary and secondary outcome measures were event-free and overall survival, respectively. Between 12-Aug-2014 and 20-Sep-2019, of the 640 R1 patients, 272 patients (136 in each group) were enrolled to R2. Median follow-up was 5.5 years. Three-year EFS was 59% in the zoledronic acid group and 57% in the no zoledronic acid group (adjusted hazard ratio = 0·92 (95% CI: 0·64, 1.31), p = 0.632). Three-year OS was 75% for both groups (adjusted hazard ratio = 0.84 (95% CI: 0.56, 1.25), p = 0.386). Adding zoledronic acid did not improve clinical outcomes in ES. The trial was prospectively registered with EudraCT 2012-002107-17 and ISRCTN 54540667.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"134 10","pages":"1393-1402"},"PeriodicalIF":6.8,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455607","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 impact of social drivers of health on delayed time to breast cancer surgery 社会健康因素对延迟乳腺癌手术时间的影响。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-14 DOI: 10.1038/s41416-026-03380-7

Shadi Azam, Anjile An, Kevin H. Kensler, Mark G. Weiner, Lauren Mount, Vivian Bea, Rulla M. Tamimi

{"title":"The impact of social drivers of health on delayed time to breast cancer surgery","authors":"Shadi Azam, Anjile An, Kevin H. Kensler, Mark G. Weiner, Lauren Mount, Vivian Bea, Rulla M. Tamimi","doi":"10.1038/s41416-026-03380-7","DOIUrl":"10.1038/s41416-026-03380-7","url":null,"abstract":"Timely surgical treatment is critical for optimal breast cancer (BC) outcomes, yet delays in care persist. This study examined associations between social drivers of health (SDOH), race/ethnicity, and delayed BC surgery in New York City, stratified by surgery type. We conducted a retrospective analysis of BC cases diagnosed between 2007 and 2021 using INSIGHT Clinical Research Network data. Neighborhood-level SDOH, including household income, unemployment, percent of non-English speakers, and high school completion, were evaluated in relation to delayed surgery (>60 days from diagnosis). Multivariable logistic regression assessed associations between (1) SDOH and (2) race/ethnicity and delay of BC surgery, adjusting for confounders. Surgical delay occurred in 10.7% of lumpectomy and 25.3% of mastectomy patients. For lumpectomy, delays were more likely in neighborhoods with the highest non-English-speaking (OR = 1.37, 95%CI = 1.12–1.68) and higher unemployment quartiles (OR = 1.49, 95%CI = 1.22–1.82) and less likely in the highest income (OR = 0.69,95%CI = 0.56–0.84) and education quartiles (OR = 0.60, 95%CI = 0.49–0.74). Mastectomy showed similar patterns. Delays were more frequent among Non-Hispanic Black (lumpectomy OR = 2.23; mastectomy OR = 1.82) and Hispanic patients (OR = 1.64; OR = 1.39). This large, multi-institutional study reveals persistent disparities in timely surgical care. Nearly 15% experienced delays, with higher odds among Non-Hispanic Black, Hispanic, and socioeconomically disadvantaged patients, underscoring the need for equity-focused interventions.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"134 9","pages":"1325-1335"},"PeriodicalIF":6.8,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455651","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

Genomic sequencing of multicystic mesothelioma finds cohesin complex mutations associated with disease recurrence in patients referred for cytoreductive surgery and HIPEC 多囊间皮瘤的基因组测序发现，在接受细胞减少手术和HIPEC的患者中，黏结蛋白复合物突变与疾病复发相关。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-14 DOI: 10.1038/s41416-026-03366-5

Jane Gibson, Norman John Carr, Sophia Stanford, Amatta Mirandari, Thomas Desmond Cecil, Reuben J. Pengelly, Steven Turner, Jonathan W. Essex, Konstantinos Boukas, Kevin Hocking, Manuel Dominguez, Faheez Mohamed, Sanjeev Paul Dayal, Alexios Tzivanakis, Brendan John Moran, Gbadebo Adeleke, Alex Mirnezami, Sarah Ennis

{"title":"Genomic sequencing of multicystic mesothelioma finds cohesin complex mutations associated with disease recurrence in patients referred for cytoreductive surgery and HIPEC","authors":"Jane Gibson, Norman John Carr, Sophia Stanford, Amatta Mirandari, Thomas Desmond Cecil, Reuben J. Pengelly, Steven Turner, Jonathan W. Essex, Konstantinos Boukas, Kevin Hocking, Manuel Dominguez, Faheez Mohamed, Sanjeev Paul Dayal, Alexios Tzivanakis, Brendan John Moran, Gbadebo Adeleke, Alex Mirnezami, Sarah Ennis","doi":"10.1038/s41416-026-03366-5","DOIUrl":"10.1038/s41416-026-03366-5","url":null,"abstract":"Multicystic mesothelioma (MCM) is a rare disease and there is debate about it’s neoplastic nature with a spectrum of disease behaviour and little known about the genomic profile. In contrast, the genomic profile of malignant peritoneal mesothelioma (MPeM) is characterised. We characterized 24 MCM and 18 MPeM cases across a panel of cancer related regions and expanded to whole-exome sequencing for 11 MCMs. Validation by amplicon sequencing and functional assessment by molecular dynamic simulation were carried out. Kaplan-Meier analysis was carried out to assess recurrence-free survival. Few mutations were identified in MCMs across the panel. Exome sequencing revealed 28 genes mutated in >1 MCM case. We saw significant overrepresentation of mutations in the cohesin complex in SMC3, SMC1A, and STAG3. Multiple mutations in SMC3 at codon p.E1144 indicated a mutational hotspot. Molecular dynamics simulations showed mutation at this site impacts the protein function. Amplicon sequencing confirmed hotspot mutations in further MCMs. We observed a significant association (p = 0.0302) of mutation in SMC3 or SMC1A with disease recurrence. We see recurrent somatic mutations in MCMs particularly at a novel mutational hotspot in SMC3, consistent with a neoplastic process. Mutations in cohesin complex genes are associated with disease recurrence.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"134 9","pages":"1352-1359"},"PeriodicalIF":6.8,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03366-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455660","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}

引用次数: 0

Enhanced nuclear export caused by O-GlcNAcylation of nucleoporins is a potential therapeutic target in mesothelioma 核孔蛋白o - glcn酰化引起的核输出增强是间皮瘤的潜在治疗靶点。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-06 DOI: 10.1038/s41416-026-03369-2

Satomi Mukai, Tatsuhiro Sato, Yasuhiro Kamei, Kagayaki Kato, Emi Mishiro-Sato, Lisa Kondo-Ida, Norikazu Yabuta, Kenzo Hiroshima, Yoshitaka Sekido

{"title":"Enhanced nuclear export caused by O-GlcNAcylation of nucleoporins is a potential therapeutic target in mesothelioma","authors":"Satomi Mukai, Tatsuhiro Sato, Yasuhiro Kamei, Kagayaki Kato, Emi Mishiro-Sato, Lisa Kondo-Ida, Norikazu Yabuta, Kenzo Hiroshima, Yoshitaka Sekido","doi":"10.1038/s41416-026-03369-2","DOIUrl":"10.1038/s41416-026-03369-2","url":null,"abstract":"Mesothelioma is an aggressive malignancy with limited therapeutic options. Genetic alterations involving the Hippo pathway are commonly observed. O-GlcNAcylation is frequently elevated in cancer and drives tumour progression. However, its relationship with Hippo pathway dysfunction in mesothelioma remains unclear. O-GlcNAcylation levels were examined in mesothelioma samples and cell lines, and O-GlcNAcylated proteins were detected by mass spectrometry. The functional impact of O-GlcNAcylation was determined by quantifying nuclear transport dynamics using light-induced live-cell imaging. Genetic and pharmacological inhibition of O-GlcNAcylation was evaluated in vitro. Treatment with the nuclear export inhibitor KPT-330 (Selinexor) was assessed in vitro and in a mouse xenograft model. O-GlcNAcylation was markedly increased in mesothelioma cells with Hippo pathway inactivation. This modification primarily targeted nuclear pore complex proteins, including NUP214 and NUP62, and significantly accelerated nuclear export rates. Suppression of O-GlcNAcylation diminished nuclear export and inhibited cell proliferation. Importantly, pharmacological blockade of nuclear export using KPT-330 suppressed cell growth in vitro and produced significant antitumour effects in vivo. These findings demonstrate O-GlcNAcylation-driven enhancement of nuclear export as a therapeutically actionable vulnerability in mesothelioma with inactivation of the Hippo pathway.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"134 9","pages":"1276-1288"},"PeriodicalIF":6.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369070","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

Investigating PAK inhibition in combination with PD-1 blockade to enhance cytotoxic CD8+ T cell-mediated killing and suppress invasion of ovarian cancer cells 研究PAK抑制联合PD-1阻断增强细胞毒性CD8+ T细胞介导的杀伤和抑制卵巢癌细胞的侵袭。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-06 DOI: 10.1038/s41416-026-03342-z

Alexandria R. Mitchell, Yiran Chen, Giuseppe Pugliese, Gabriela Vino Flores, David M. Davies, John Maher, Claire M. Wells

{"title":"Investigating PAK inhibition in combination with PD-1 blockade to enhance cytotoxic CD8+ T cell-mediated killing and suppress invasion of ovarian cancer cells","authors":"Alexandria R. Mitchell, Yiran Chen, Giuseppe Pugliese, Gabriela Vino Flores, David M. Davies, John Maher, Claire M. Wells","doi":"10.1038/s41416-026-03342-z","DOIUrl":"10.1038/s41416-026-03342-z","url":null,"abstract":"P-21 activated kinase (PAK) overexpression, phosphorylation, and gene amplification have been reported to increase cellular invasion in ovarian cancer (ovcan), worsening patient prognoses. One notable method of ovcan survival is through the PD-(L)1 checkpoint pathway, and PD-L1 expression in ovcan is correlated with poor patient outcomes. However, PD-1 and PD-L1 targeted clinical trials in ovcan have shown modest results. This work has examined the possibility of using PAKi and PD-1 blockade as a combination therapy. PAK and PD-L1 expression in ovarian cells was determined. A novel 3D spheroid assay was used to assess ovcan invasion. Ovcan cell viability, downstream pathway signalling, and surface PD-L1 expression were evaluated after treatment with PAK inhibitors and co-culture with cytotoxic CD8+ T cells. Ovcan cell and CD8+ T cell co-cultures were treated with a combination of PAK inhibition and PD-1 checkpoint blockade and ovcan cell viability was assessed. Ovcan cells showed significant sensitivity to PAKi. CD8+ T cell killing of ovcan cells improved following pre-treatment with PAK inhibitors, and this was further augmented with PD-1 blockade. The work presented here demonstrates the efficacy of PAK inhibition and PD-1 checkpoint blockade as a combination therapy for high-grade serous ovarian cancer.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"134 9","pages":"1248-1260"},"PeriodicalIF":6.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03342-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369024","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}

引用次数: 0

Dynamic reorganisation of intratumoural bacterial florae during colorectal cancer progression 结直肠癌进展过程中肿瘤内菌群的动态重组。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-06 DOI: 10.1038/s41416-026-03344-x

Minghao Li, Yang Li, Chen Li, Anhang Liu, Yang Liu, Yang Li, Jian Xiao, Dongchen Zhang, Yan Jin, Guangxi Wang, Xin Pang, Kewei Jiang, Yuxin Yin

{"title":"Dynamic reorganisation of intratumoural bacterial florae during colorectal cancer progression","authors":"Minghao Li, Yang Li, Chen Li, Anhang Liu, Yang Liu, Yang Li, Jian Xiao, Dongchen Zhang, Yan Jin, Guangxi Wang, Xin Pang, Kewei Jiang, Yuxin Yin","doi":"10.1038/s41416-026-03344-x","DOIUrl":"10.1038/s41416-026-03344-x","url":null,"abstract":"Colorectal cancer (CRC) exhibits distinct bacterial community compositions compared to healthy mucosae, which intimately correlate with CRC clinical outcomes. There is a lack of explanation for the inducements of microbiota remodelling. FISH experiments and 16S rRNA sequencing were conducted to determine the inducements of various bacterial colonisation within tissues. Community cultivation was conducted to estimate the capacity of tumours to remodel bacterial communities. Metagenomic analyses were utilised to determine the remodelled communities of CRC with distant metastasis. Scratch tests and three-dimensional (3D) cultivation were employed to investigate the influence of specific taxa on tumour cell behaviours. Colorectal tumours exhibit heterogeneous and individualised preferences in constantly remodelling intratumoural bacterial florae. Various degrees of colorectal gland differentiation within tumours cause heterogeneous intratumoural bacterial colonisation. CRC progression further alters bacterial community composition. Particularly, Prevotella is significantly enriched in the newly established communities colonising the primary foci of metastatic CRC. Furthermore, Prevotella intermedia (P. intermedia) promotes the invasion, migration, and ectopic tumorigenesis of CRC cells. Individual evaluation of the preference of tumours in microbiota may pave the way to the development of CRC therapeutic strategies, and Prevotella is an emerging genus worthy of clinical attention.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"134 9","pages":"1261-1275"},"PeriodicalIF":6.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369089","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