British Journal of Cancer最新文献_第8页

Value of whole-body diffusion-weighted MRI for the prediction of surgical and clinical outcome after neoadjuvant chemotherapy in advanced ovarian cancer. 全身弥散加权MRI对晚期卵巢癌新辅助化疗后手术及临床预后的预测价值。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-04-04 DOI: 10.1038/s41416-026-03383-4

Vincent Vandecaveye, Raphaëla C Dresen, Thaïs Baert, Valérie Broeckhoven, Els Van Nieuwenhuysen, Toon Van Gorp, Frederik De Keyzer, Ignace Vergote

{"title":"Value of whole-body diffusion-weighted MRI for the prediction of surgical and clinical outcome after neoadjuvant chemotherapy in advanced ovarian cancer.","authors":"Vincent Vandecaveye, Raphaëla C Dresen, Thaïs Baert, Valérie Broeckhoven, Els Van Nieuwenhuysen, Toon Van Gorp, Frederik De Keyzer, Ignace Vergote","doi":"10.1038/s41416-026-03383-4","DOIUrl":"https://doi.org/10.1038/s41416-026-03383-4","url":null,"abstract":"Background: Prediction of surgical and survival outcomes following neoadjuvant chemotherapy (NACT) in ovarian cancer remains challenging. This study evaluated whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) after NACT for predicting complete resection at interval debulking surgery (IDS), progression-free survival, and overall survival.Methods: In this prospective, single-centre study, 105 patients with non-primary resectable ovarian cancer underwent WB-DWI/MRI following NACT. The performance of WB-DWI/MRI in predicting complete resection and survival was assessed. Prediction of complete resection was compared with computed tomography (CT) when available.Results: Seventy-four (70%) patients achieved complete resection. WB-DWI/MRI-predicted complete resection with 97.3% sensitivity, 83.9% specificity and 93.3% accuracy. MRI-based complete resection prediction, complete resection at IDS, and serum CA-125 significantly affected progression-free survival (MRI: Hazard Ratio [HR] = 5.43, IDS: HR = 4.19, CA-125: HR = 1.68; p < 0.01) with the first two parameters also significantly affecting overall survival (MRI: HR = 4.24, IDS: HR = 2.87; p < 0.01). Multivariate analysis confirmed MRI-based complete resection prediction and serum CA-125 as significant for progression-free (p < 0.001 and p = 0.04) and MRI-based prediction significant for overall survival (p < 0.001). In a 69-patient subanalysis, WB-DWI/MRI-predicted complete resection was significantly better than CT (91.3% vs. 72.5% accuracy, p < 0.001).Conclusion: WB-DWI/MRI after NACT is accurate for predicting surgical and survival outcomes in patients with non-primary resectable ovarian cancer.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618538","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

TCF3::HLF-positive B-ALL: integrated clinical and molecular characterization of 34 cases from a single-center cohort. TCF3:: hlf阳性B-ALL：来自单中心队列的34例患者的综合临床和分子特征

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-04-04 DOI: 10.1038/s41416-026-03370-9

Xue Chen, Xiaoli Ma, Lili Yuan, Fang Wang, Yang Zhang, Jiancheng Fang, Panxiang Cao, Tong Wang, Min Xiong, Junfang Yang, Xian Zhang, Jiaqi Chen, Xiaosu Zhou, Siyuan Liu, Hongxing Liu

{"title":"TCF3::HLF-positive B-ALL: integrated clinical and molecular characterization of 34 cases from a single-center cohort.","authors":"Xue Chen, Xiaoli Ma, Lili Yuan, Fang Wang, Yang Zhang, Jiancheng Fang, Panxiang Cao, Tong Wang, Min Xiong, Junfang Yang, Xian Zhang, Jiaqi Chen, Xiaosu Zhou, Siyuan Liu, Hongxing Liu","doi":"10.1038/s41416-026-03370-9","DOIUrl":"https://doi.org/10.1038/s41416-026-03370-9","url":null,"abstract":"Background: TCF3::HLF-positive B-cell acute lymphoblastic leukemia (B-ALL) is a rare, highly aggressive subtype with historically poor outcomes. Despite its classification as a distinct entity, its clinical and molecular landscape remains poorly understood.Methods: This study presents a single-center cohort of 34 TCF3::HLF-positive B-ALL patients, providing comprehensive clinical and molecular characterization by integrating clinical data, treatment responses, survival outcomes, whole-transcriptome sequencing (WTS), targeted sequencing, and flow cytometry.Results: TCF3::HLF accounted for 1.59% of B-ALL cases. Three fusion isoforms were identified, with Isoform III likely arising from alternative splicing. No significant clinical or transcriptomic differences were observed between Isoform I and II. The 5-year overall survival (OS) was 35.2%. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved OS and event-free survival (p < 0.0001), while chimeric antigen receptor T-cell (CAR-T) therapy facilitated allo-HSCT but lacked durable efficacy. RAS pathway mutations were prevalent (85.7%), and CD33 expression was frequent (79.4%), suggesting potential therapeutic targets. WTS analysis revealed dysregulation of epithelial-mesenchymal transition, coagulation, and immune pathways.Conclusions: TCF3::HLF-positive B-ALL represents an ultra-high-risk leukemia requiring allo-HSCT for long-term remission. CAR-T serves as a bridge to transplantation, while RAS and CD33-directed therapies warrant further investigation. These findings provide critical insights into disease biology and potential treatment.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618528","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

Nuclear FGF2, androgen receptor and Wnt pathway activation define a targetable subset of antiprogestin-resistant luminal breast cancer. 核FGF2、雄激素受体和Wnt通路激活定义了抗孕激素耐药腔内乳腺癌的可靶向亚群。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-04-04 DOI: 10.1038/s41416-026-03420-2

Virginia Figueroa, Marcela I Coianis, Ana Sahores, Gabriela Pataccini, Martín C Abba, Andrés Elía, María May, Silvia I Vanzulli, Paula Martínez Vázquez, Javier Burruchaga, Florencia Torres, Carol A Sartorius, Claudia Lanari, Caroline A Lamb

{"title":"Nuclear FGF2, androgen receptor and Wnt pathway activation define a targetable subset of antiprogestin-resistant luminal breast cancer.","authors":"Virginia Figueroa, Marcela I Coianis, Ana Sahores, Gabriela Pataccini, Martín C Abba, Andrés Elía, María May, Silvia I Vanzulli, Paula Martínez Vázquez, Javier Burruchaga, Florencia Torres, Carol A Sartorius, Claudia Lanari, Caroline A Lamb","doi":"10.1038/s41416-026-03420-2","DOIUrl":"https://doi.org/10.1038/s41416-026-03420-2","url":null,"abstract":"Background: Endocrine resistance is a major clinical challenge in luminal breast cancer. Nuclear fibroblast growth factor 2 (FGF2) and altered progesterone receptor (PR) isoform ratios have been identified as markers of antiprogestin resistance. We investigated pathways associated with FGF2 upregulation to identify new targets for antiprogestin-resistant tumours.Methods: PR+ T47D and T47D‑YA cell lines engineered to overexpress FGF2 were used to investigate FGF2‑driven antiprogestin resistance. Transcriptome profiling, qRT-PCR, immunohistochemistry, and in vivo assays assessed hormone receptor expression, pathway alterations, and therapeutic response. We evaluated nuclear androgen receptor (AR) and FGF2 in luminal breast cancer specimens.Results: RNA-seq showed that FGF2 overexpression dysregulated Wnt signalling, downregulated oestrogen receptor (ER) and PR, and upregulated AR expression. PR isoform B (PRB) predominated, consistent with an antiprogestin-resistant phenotype. FGF2-overexpressing xenografts showed antiprogestin resistance, increased proliferation, and lung metastasis. AR and Wnt pathway blockade impaired tumour growth, and combined treatment further reduced tumour and metastatic burden. In clinical samples, nuclear FGF2 correlated with elevated AR levels in ER+PR- and PRB-high tumours.Conclusion: We identified a subset of luminal breast cancers characterised by nuclear FGF2, AR upregulation, and PR isoform imbalance. Dual AR and Wnt pathway targeting may offer a promising strategy for antiprogestin-resistant disease.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618576","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

Treatment monitoring by biomarker analysis in a Phase I dose-expansion study of AZD2811 for relapsed/refractory small-cell lung cancer. AZD2811治疗复发/难治性小细胞肺癌的I期剂量扩展研究中生物标志物分析的治疗监测

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-04-03 DOI: 10.1038/s41416-026-03414-0

Melissa L Johnson, Giulia Fabbri, Carmela Ciardullo, Judy S Wang, Gerald S Falchook, Suzanne Jones, Donald Strickland, Jacob Sands, Carl M Gay, Robert J Cardnell, Luis Tobalina, Sophie E Willis, Jaime Rodriguez-Canales, Myria Nikolaou, Emma V Jones, Stein Schalkwijk, Liz Sainsbury, Alexander MacDonald, Philip Overend, Caroline Kennedy, J Elizabeth Pease, Philip Szekeres, Jan Cosaert, Howard Burris, Lauren A Byers

{"title":"Treatment monitoring by biomarker analysis in a Phase I dose-expansion study of AZD2811 for relapsed/refractory small-cell lung cancer.","authors":"Melissa L Johnson, Giulia Fabbri, Carmela Ciardullo, Judy S Wang, Gerald S Falchook, Suzanne Jones, Donald Strickland, Jacob Sands, Carl M Gay, Robert J Cardnell, Luis Tobalina, Sophie E Willis, Jaime Rodriguez-Canales, Myria Nikolaou, Emma V Jones, Stein Schalkwijk, Liz Sainsbury, Alexander MacDonald, Philip Overend, Caroline Kennedy, J Elizabeth Pease, Philip Szekeres, Jan Cosaert, Howard Burris, Lauren A Byers","doi":"10.1038/s41416-026-03414-0","DOIUrl":"https://doi.org/10.1038/s41416-026-03414-0","url":null,"abstract":"Background: Aurora kinase B (AURKB) is overexpressed in lung cancer and is associated with poor prognosis. AZD2811 is an AURKB inhibitor that demonstrated tolerability during a Phase I dose-escalation study in patients with advanced solid tumours, including small-cell lung cancer (SCLC). Here we report the dose-expansion results.Methods: Eligible patients received nanoparticle-formulated AZD2811 500 mg IV (Day 1; 21-day cycles) with granulocyte colony-stimulating factor (Day 8). Dose-expansion endpoints included: preliminary antitumour activity, safety/tolerability, pharmacokinetics, and biomarker-based disease monitoring.Results: One of 21 enrolled patients achieved a partial response for an objective response rate of 4.8%; stable disease ≥6 weeks was observed in 10 patients (47.6%). The most common AZD2811-related AEs were decreased neutrophil and white blood cell count, anaemia, and decreased platelet count; grade ≥3 AZD2811-related AEs occurred in 15/21 patients. Baseline ctDNA levels were prognostic, and on-treatment ctDNA changes mirrored clinical response and identified progression early, suggesting it could be an effective surrogate for tumour tissue. Molecular profiling of paired tumour biopsies demonstrated AZD2811 pharmacodynamic activity and identified genes/pathways potentially linked to response.Conclusion: A personalised surveillance strategy may provide a novel avenue to monitor SCLC, supporting further investigation and potential broader clinical application.Clinical trial registration: NCT02579226.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615862","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

Molecular phenotypes stratify small cell lung cancer for targeted therapy and immunotherapy. 分子表型分层小细胞肺癌靶向治疗和免疫治疗。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-04-03 DOI: 10.1038/s41416-026-03390-5

Juxuan Zhang, Yiyan Liu, Hengrui Yuan, Ning Zhan, Jiaxing Deng, Lefan Tang, Xin Li, Yixin Liu, Wenyuan Zhao, Shilong Liu, Lishuang Qi

{"title":"Molecular phenotypes stratify small cell lung cancer for targeted therapy and immunotherapy.","authors":"Juxuan Zhang, Yiyan Liu, Hengrui Yuan, Ning Zhan, Jiaxing Deng, Lefan Tang, Xin Li, Yixin Liu, Wenyuan Zhao, Shilong Liu, Lishuang Qi","doi":"10.1038/s41416-026-03390-5","DOIUrl":"https://doi.org/10.1038/s41416-026-03390-5","url":null,"abstract":"Background: Small cell lung cancer (SCLC), an aggressive neuroendocrine malignancy, exhibits high intertumoral heterogeneity and limited treatment options. Immune checkpoint inhibitors (ICIs) provide only modest benefits for SCLC, underscoring the need for clinically actionable phenotypes.Methods: Consensus clustering of bulk transcriptomic data identified SCLC molecular phenotypes. Bulk and single-cell RNA sequencing (scRNA-seq) revealed their molecular and immune characteristics, as well as tumor microenvironment interactions. Survival benefits of ICIs were assessed in 41 newly collected extensive-stage SCLC (ES-SCLC) patients treated with chemotherapy plus ICIs, integrated with a public dataset.Results: We identified three distinct SCLC phenotypes, termed proliferative, iNotch, and infiltrated phenotypes, as they were characterized by high proliferation, inhibitory Notch signaling, and immune-rich microenvironments, respectively. These phenotypes were reproducible across three bulk independent datasets. Further intercellular communication analysis of scRNA-seq data revealed a subset with high ANXA1 expression in the infiltrated phenotype suppressed CD8+ T cells via M2 macrophage polarization. Survival analyses showed that only ANXA1Low infiltrated patients derived significant survival benefit from chemotherapy plus ICIs.Conclusions: This study identified three distinct SCLC phenotypes with unique therapeutic vulnerabilities. An ANXA1High subset within the immune-rich infiltrated phenotype showed ICI resistance, offering new strategies to enhance ICI efficacy.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615912","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

Faecal haemoglobin-based referral and investigation prioritisation is associated with colorectal cancer-specific survival in symptomatic patients: a retrospective observational study. 基于粪便血红蛋白的转诊和调查优先级与有症状患者的结直肠癌特异性生存率相关：一项回顾性观察性研究

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-04-02 DOI: 10.1038/s41416-026-03378-1

Stephen T McSorley, Paul Burton, Donna Chantler, Mark Johnstone, Brian D Nicholson, Graham MacKay, David Mansouri, Mark Vella, Susanti Susanti, Douglas Rigg, Jack Winter, Paul Witherspoon

{"title":"Faecal haemoglobin-based referral and investigation prioritisation is associated with colorectal cancer-specific survival in symptomatic patients: a retrospective observational study.","authors":"Stephen T McSorley, Paul Burton, Donna Chantler, Mark Johnstone, Brian D Nicholson, Graham MacKay, David Mansouri, Mark Vella, Susanti Susanti, Douglas Rigg, Jack Winter, Paul Witherspoon","doi":"10.1038/s41416-026-03378-1","DOIUrl":"https://doi.org/10.1038/s41416-026-03378-1","url":null,"abstract":"Background: Current BSG/ACPGBI and NICE guidance recommends that faecal haemoglobin (f-Hb) ≥10 ug/g measured by faecal immunochemical test (FIT) in symptomatic patients should prompt referral through cancer prioritised diagnostic pathways. However, limited long term CRC outcome data exist. This study compared CRC specific survival (CSS) between patients by f-Hb concentration and referral priority in a large primary care f-Hb prioritised lower GI symptomatic pathway.Methods: Retrospective single health board study of symptomatic patients submitting FIT in primary care, 2019-2022. CRC diagnoses up to 3 years after pathway entry, and CRC deaths (ICD10 18, 19, 20) to end 2024 were recorded from cancer audit and MCN datasets. Patients were grouped by f-Hb concentration and referral priority. Univariable and multivariable Cox regression estimated CSS.Result: Of 126,984 patients, 1453 (1%) were diagnosed with CRC within 3 years of f-Hb result or referral, of which 444 (31%) died due to CRC. At multivariable analysis, referral without FIT (HR 1.42, 95% CI 1.06-1.91), and f-Hb ≥10 ug/g diagnosed outwith CRC prioritised pathways (HR 1.47, 95% CI 1.03-2.10) were associated with worse CSS independent of TNM stage.Conclusion: Referral and investigation through cancer prioritised pathways guided by f-Hb concentration is safe in relation to CSS.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608246","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

Incorporating early cfEBV DNA clearance into clinical risk stratification to tailor induction chemotherapy cycles for locoregionally advanced nasopharyngeal carcinoma. 将早期cfEBV DNA清除纳入临床风险分层，以定制局部区域晚期鼻咽癌的诱导化疗周期。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-31 DOI: 10.1038/s41416-026-03401-5

Wan-Ping Guo, Xuan Yu, Zi-Jian Lu, Yu-Chen Li, Chun Wu, Li-Wen Gu, Jing-Na Cao, Dong-Hua Luo, Sai-Lan Liu, Ling Guo

{"title":"Incorporating early cfEBV DNA clearance into clinical risk stratification to tailor induction chemotherapy cycles for locoregionally advanced nasopharyngeal carcinoma.","authors":"Wan-Ping Guo, Xuan Yu, Zi-Jian Lu, Yu-Chen Li, Chun Wu, Li-Wen Gu, Jing-Na Cao, Dong-Hua Luo, Sai-Lan Liu, Ling Guo","doi":"10.1038/s41416-026-03401-5","DOIUrl":"https://doi.org/10.1038/s41416-026-03401-5","url":null,"abstract":"Background: The optimal number of induction chemotherapy (IC) cycles for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is debated. This study investigates if early cell-free Epstein-Barr virus (cfEBV) DNA clearance can personalise treatment.Methods: We included 1590 LA-NPC patients treated with IC+ chemoradiotherapy (2010-2023) with complete early cfEBV DNA data. COX regression identified independent prognostic factors, and receiver operating characteristic curves assessed predictive accuracy. Propensity score matching (PSM) balanced covariates between groups receiving different IC cycles. The primary outcome, progression-free survival (PFS) was analysed using Kaplan-Meier and log-rank tests.Results: After the first IC cycle, 45.5% of patients had undetectable cfEBV DNA. Combining cfEBV DNA clearance, N-stage, and overall stage yielded the highest AUC for 5-year PFS (0.632). Patients were stratified into high- and low-risk groups (p < 0.001). Post-matching, low-risk patients receiving three IC cycles had better 5-year PFS than those receiving two (85.2% vs. 76.0%, p = 0.024), with no significant increase in grade 3-4 toxicities (30.36% vs. 24.29%, p = 0.157). High-risk patients showed no PFS benefit from additional cycles (63.2% vs. 61.0%, p = 0.960).Discussion: Early cfEBV DNA clearance predicts LA-NPC outcomes. Low-risk patients may benefit from an additional cycle of IC, while high-risk patients may require alternative strategies like immunotherapy or earlier chemoradiotherapy.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590104","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

Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC. ATR激酶抑制剂ceralasertib与durvalumab联合用于复发或转移性NSCLC或HNSCC患者的i期研究。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-31 DOI: 10.1038/s41416-026-03408-y

Juanita S Lopez, Kevin J Harrington, Seock-Ah Im, Keun-Wook Lee, Sophie Postel-Vinay, Jacob S Thomas, Natalia Lukashchuk, Sophie E Willis, Itziar Irurzun-Arana, Benjamin Webb, Jyoti Nehra, Alan Lau, Arsène-Bienvenu Loembé, Emma Dean, Matthew G Krebs

{"title":"Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC.","authors":"Juanita S Lopez, Kevin J Harrington, Seock-Ah Im, Keun-Wook Lee, Sophie Postel-Vinay, Jacob S Thomas, Natalia Lukashchuk, Sophie E Willis, Itziar Irurzun-Arana, Benjamin Webb, Jyoti Nehra, Alan Lau, Arsène-Bienvenu Loembé, Emma Dean, Matthew G Krebs","doi":"10.1038/s41416-026-03408-y","DOIUrl":"https://doi.org/10.1038/s41416-026-03408-y","url":null,"abstract":"Background: This multicentre, modular, Phase 1 study evaluated escalating doses of ATR (ataxia telangiectasia and Rad3-related kinase) inhibitor ceralasertib plus PD-L1 inhibitor durvalumab in patients with previously treated advanced/metastatic non-small-cell lung cancer (NSCLC) or head and neck squamous cell carcinoma (HNSCC).Methods: Patients received ceralasertib 80/160/240 mg twice-daily (BID) or 320 mg once-daily (QD) for 7 (Days 22-28) or 14 (Days 15-28) days, plus durvalumab 1500 mg (Day 1), per 28-day cycle. The primary objective was to investigate the safety/tolerability of the combination.Results: Sixty patients were treated. Two patients had dose-limiting toxicities of: Grade 3 thrombocytopenia with Grade 3 anaemia (ceralasertib 320 mg QD for 14 days); and Grade 4 thrombocytopenia with Grade 3 neutropenia accompanied by systemic chest infection (ceralasertib 240 mg BID for 14 days). Overall, 59 (98.3%) patients had treatment-emergent adverse events; 31 (51.7%) had grade ≥3 events. The recommended Phase 2 dose was durvalumab 1500 mg (Day 1) plus ceralasertib 240 mg BID (Days 15-28). Five (8.3%) patients had objective responses; 31 (51.7%) had stable disease. Pharmacodynamic activity (pRAD50 increase) was observed in 10/14 paired biopsies.Conclusion: Ceralasertib plus durvalumab was tolerated and associated with antitumour activity in advanced/metastatic NSCLC and HNSCC.Trial registration number: NCT02264678.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590146","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

Sarcopenia and cancer outcomes: thresholds need to account for age-related changes in muscle mass 肌肉减少症和癌症结局：阈值需要考虑与年龄相关的肌肉质量变化。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-30 DOI: 10.1038/s41416-026-03382-5

James Cairns, Russell Frood, Andrew Scarsbrook, Andrew G Renehan

引用次数: 0

Correction: Exploratory analysis of gene aberrations and chemotherapy response: findings from a real-world database in Japan 修正：基因畸变和化疗反应的探索性分析：来自日本真实世界数据库的发现。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-03-30 DOI: 10.1038/s41416-026-03377-2

Naoya Ishibashi, Takashi Kamatani, Satoru Aoyama, Masanori Tokunaga, Yusuke Kinugasa, Sadakatsu Ikeda

引用次数: 0