British Journal of Cancer最新文献

{"title":"A plasma derived hypoxia signature predicts benefit from hypoxia-modifying radiotherapy and reveals dynamic humoral immune modulation in bladder cancer.","authors":"C Guerrero Quiles, H Abumanhal-Masarweh, J G Abalos, T Lodhi, D Sanchez-Martinez, K Reeves, Nicholas D James, Emma Hall, Robert A Huddart, Nuria Porta, P Hoskin, L V Biolatti, M Hadjidemetriou, C M West, A Choudhury","doi":"10.1038/s41416-026-03603-x","DOIUrl":"https://doi.org/10.1038/s41416-026-03603-x","url":null,"abstract":"<p><strong>Introduction: </strong>Hypoxia is a hallmark of solid tumours and drives radioresistance, yet no hypoxia biomarkers are used clinically. We explored nanoproteomics to identify a plasma protein signature for longitudinal non-invasive hypoxia monitoring.</p><p><strong>Methods: </strong>Twenty-three bladder cancer patients (T2-T3b) undergoing radiotherapy (55 Gy, 4 weeks) were prospectively enroled. Plasma was collected at baseline and weekly, nanoparticle-enriched and analysed by proteomics. Hypoxia scores (HS) were derived from diagnostic biopsies using a validated 24-gene signature, and patients stratified by median HS.</p><p><strong>Results: </strong>We identified 115 differentially abundant proteins (DAPs; |FC | > 1.5; p < 0.05). Seven DAPs (IGKV3, IGLV2-18, VL_4, VL_7, FN1, IGLV2-14, CAMP) correlated with HS across multiple timepoints (p < 0.05; |r | >0.4). A two-protein signature (FN1, CAMP) was retrospectively validated, showing prognostic value in TCGA-BLCA (n = 404; HR = 1.54; CI = 1.12-2.13; p = 0.009), BC2001 (n = 313; HR = 1.42; CI = 1.08-1.86; p = 0.011) and in meta-analysis (n = 150; HR = 1.48; CI = 1.23-1.78; p < 0.001). In BCON (n = 150), it predicted benefit from hypoxia-modifying therapy (HR = 0.60; CI = 0.34-1.06; p = 0.079). The 115 DAPs formed five temporal co-expression clusters peaking at successive treatment weeks. Clusters were enriched for humoral immune pathways, with one linked to extracellular matrix remodelling.</p><p><strong>Conclusion: </strong>These findings support the use of low abundance plasma biomarkers for real-time hypoxia stratification, revealing dynamic immune responses during radiotherapy associated with hypoxia.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small extracellular vesicles from the plasma of head and neck cancer patients induce dysfunctional T cell phenotypes.","authors":"Luisa Tengler, Edwin K Jackson, Karen Bieback, Ralph Röth, Stefanie Mellein, Johann Kern, Marie-Nicole Theodoraki, Julia Schütz, Lena Huber, Claudia Scherl, Nicole Rotter, Annette Affolter, Sonja Ludwig","doi":"10.1038/s41416-026-03606-8","DOIUrl":"https://doi.org/10.1038/s41416-026-03606-8","url":null,"abstract":"<p><strong>Background: </strong>Head and neck cancer (HNC) is highly immunosuppressive. Despite advances with immune checkpoint (IC) inhibitors, many HNC patients fail to respond. Tumour-derived small extracellular vesicles (sEVs) may contribute to immune evasion and therapy resistance, possibly by altering T-cell phenotypes.</p><p><strong>Method: </strong>Plasma sEVs were isolated from HNC patient samples and controls via size-exclusion chromatography. The plasma sEVs were characterised and analysed for their effects on CD4⁺ and CD8⁺ T-cell function, IC levels and gene expression.</p><p><strong>Results: </strong>HNC patient-derived sEVs inhibit CD4⁺ and CD8⁺ T-cell function and promote CD8⁺ T-cell apoptosis, correlating with disease progression. Plasma sEVs can enhance the conversion of ATP to AMP and modulate the expression of ectonucleotidases. IC profiling revealed complex alterations, with CD4⁺ T cells showing increased TIGIT and CTLA-4 but decreased BTLA, PD-1, and LAG-3 expression, whereas CD8⁺ T cells showed a downregulation of both inhibitory and stimulatory ICs. PD-1 blockade did not completely prevent sEV-mediated T-cell suppression.</p><p><strong>Conclusions: </strong>Our findings suggest that plasma sEVs contribute to systemic immune modulation in HNC by inducing dysfunctional T-cell phenotypes. The ability of plasma-derived sEVs to modulate IC expression on T cells underscores the need for further investigation into their relevance for immunotherapeutic strategies in HNC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Safety and efficacy of lapatinib, binimetinib, and vinorelbine for RAS mutant metastatic colorectal cancer: results of the RASTRIC Phase I/II trial","authors":"Maarten A. Huismans,&nbsp;Eelke H. Gort,&nbsp;Lisa T. van der Heijden,&nbsp;Sermin M. Guven Mese,&nbsp;Helena M. Klein Wolterink,&nbsp;Manon N. G. J. A. Braat,&nbsp;Sjoerd G. Elias,&nbsp;Filip Y. F. L. de Vos,&nbsp;Lot A. Devriese,&nbsp;Henk M. W. Verheul,&nbsp;Frans L. Opdam,&nbsp;Miriam Koopman,&nbsp;Hilde H. Nienhuis,&nbsp;Heleen A. Crommelin,&nbsp;Hugo J. G. Snippert,&nbsp;Alwin D. R. Huitema,&nbsp;Jeanine M. L. Roodhart","doi":"10.1038/s41416-026-03616-6","DOIUrl":"10.1038/s41416-026-03616-6","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1554-1554"},"PeriodicalIF":7.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03616-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of GC001: an oncolytic vaccinia virus expressing STRIP1 shRNA.","authors":"Gongchu Li, Gaohui Jiang, Wei Pang, Zheqi Cai, Ruikang Liu, Huiwei Zhang, Jili Zhu, Jiawei Su, Borong Zhu, Jianlei Yu, Hualin Feng, Ying Zhu, Guohui Zhang, Weizhe Xu, Ting Ye, Kan Chen, Yanrong Zhou, Dongsheng Pan, Li Sun, Zhe Qu, Xingchao Geng, Xin Wang, Yunshan Ning","doi":"10.1038/s41416-026-03618-4","DOIUrl":"https://doi.org/10.1038/s41416-026-03618-4","url":null,"abstract":"<p><strong>Background: </strong>GC001, a thymidine kinase deleted oncolytic vaccinia virus expressing striatin-interacting protein 1 (STRIP1) shRNA, has been approved by National Medical Products Administration (NMPA) of China to enter phase I clinical trial in 2023.</p><p><strong>Methods: </strong>Anti-tumour efficacy of GC001 across multiple cancer types was evaluated in mouse xenograft models. Anti-tumour immune responses were investigated in immunocompetent or humanised cancer mouse model. The mechanism of GC001 activity was elucidated including ROS accumulation, NRF2 degradation, and mitochondrial metabolic reprogramming.</p><p><strong>Results: </strong>GC001 showed potent and broad-spectrum anti-tumour activity across multiple mouse xenograft models, and stimulated anti-tumour immune responses in both immunocompetent and humanised mouse models. Importantly, GC001 did not elicit significant toxicity and was well tolerated in the nonhuman primate model. Mechanistically, GC001 induced ROS accumulation, which was driven by NRF2 degradation and mitochondrial metabolic reprogramming through the combinatorial activity of STRIP1 knockdown and oncolytic vaccinia virus backbone, whereas STRIP1 knockdown alone did not induce ROS accumulation.</p><p><strong>Conclusions: </strong>Our study reveals dual mechanisms of GC001: viral replication and cytotoxicity potentiation through ROS-Hippo pathway, and oxidative stress-mediated anti-tumour immune responses. Studies have demonstrated robust anti-tumour efficacy and favourable safety profile of GC001, thereby establishing it as a promising oncolytic VV candidate for clinical development.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERa-induced m⁶A reader HNRNPC maintains DDX6 mRNA stability to promote tumor progression in ER+BC.","authors":"Ziwei Huang, Wenjie Xu, Yunxiao Xiao, Wenhui Li, Ming Xu, Qiuyang Zhao, Pengfei Yi","doi":"10.1038/s41416-026-03506-x","DOIUrl":"https://doi.org/10.1038/s41416-026-03506-x","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) remains a major threat to women's health globally. The RNA m6A modification and its readers, such as heterogeneous nuclear ribonucleoprotein C (HNRNPC), which is upregulated in multiple cancers, play critical roles in tumorigenesis.</p><p><strong>Methods: </strong>We assessed gene/protein expression (RT-qPCR, western blot) and cellular functions. Molecular mechanisms involving HNRNPC, DDX6, and m6A modifications were deciphered using RIP, meRIP, ChIP, and RNA pull-down assays. The oncogenic role of HNRNPC was confirmed in xenograft models.</p><p><strong>Results: </strong>We found that HNRNPC has an abnormally high expression in BC, and knocking down HNRNPC could inhibit the tumor progression of BC. RNA immunoprecipitation revealed that HNRNPC could recognize and bind to the continuous \"U\" region in 3'UTR of m6A-modified DEAD-Box helicase 6 (DDX6) in the nucleus, which maintains the stability of DDX6 mRNA. Besides, estrogen receptor (ER) α could serve as a transcription factor and bind to the promoter site of HNRNPC, which up-regulated HNRNPC expression.</p><p><strong>Discussion: </strong>We unveiled an ERα/HNRNPC/DDX6 axis in ER+ breast cancer, wherein ERα transcriptionally upregulates HNRNPC, which in turn stabilizes DDX6 mRNA in an m6A-dependent manner to drive tumor progression, suggesting HNRNPC as a promising therapeutic target.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproductive factors and the expression of stromal markers in benign breast biopsy samples.","authors":"Maisey Ratcliffe, Yujing J Heng, Yaileen D Guzman-Arocho, Bernard Rosner, Rulla M Tamimi, Lusine Yaghjyan","doi":"10.1038/s41416-026-03615-7","DOIUrl":"https://doi.org/10.1038/s41416-026-03615-7","url":null,"abstract":"<p><strong>Background: </strong>We examined the associations of several reproductive factors with expression of stromal fibroblast markers αSMA, TNC, FAP, S100A6, and MMP14.</p><p><strong>Methods: </strong>We included 694 cancer-free women with biopsy-confirmed incident benign breast disease within the Nurses' Health Study II. Breast cancer risk factor data were obtained from biennial questionnaires. Immunofluorescence of stromal markers was completed on tissue microarrays. For each core, % positivity was quantified with inForm v2.6.0. Generalized linear regression was used to examine the associations of reproductive factors with log-transformed positivity for each marker.</p><p><strong>Results: </strong>In multivariate analysis, nulliparous status showed a suggestive positive association with TNC expression (β = 0.79, 95% CI -0.10, 1.68, p = 0.08) but was not associated with the other stromal markers (all p > 0.10). No associations were seen for number of children, age at 1st birth, breastfeeding, continuous age at menarche, time between menarche and age at first birth, and time since last birth with any of the markers' expression. Categorical age at menarche showed a suggestive positive association with MMP14 (p-trend = 0.07).</p><p><strong>Conclusion: </strong>Our findings suggest that nulliparous status and age at menarche may be associated with the expression of stromal fibroblast activation markers TNC and MMP14, respectively. Further studies are needed to confirm these findings.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological considerations in defining CBL as a prognostic biomarker in stage II melanoma","authors":"Jingyi Han,&nbsp;Xinger Gao,&nbsp;Wenjun Jiang","doi":"10.1038/s41416-026-03628-2","DOIUrl":"10.1038/s41416-026-03628-2","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1357-1358"},"PeriodicalIF":7.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory biomarkers and risk of postmenopausal oestrogen receptor-positive breast cancer: a case-cohort analysis.","authors":"Frances Em Albers, Christopher Tv Swain, S Ghazaleh Dashti, Sabina Rinaldi, Vivian Viallon, Amalia Karahalios, Kristy A Brown, Marc J Gunter, Roger L Milne, Dallas R English, Brigid M Lynch","doi":"10.1038/s41416-026-03624-6","DOIUrl":"https://doi.org/10.1038/s41416-026-03624-6","url":null,"abstract":"<p><strong>Background: </strong>The role of systemic inflammation in postmenopausal breast carcinogenesis remains unclear. Using a case-cohort study within the Melbourne Collaborative Cohort Study, we estimated the effects of circulating inflammatory biomarkers on the risk of postmenopausal oestrogen receptor (ER)-positive breast cancer.</p><p><strong>Methods: </strong>We included 1223 females (347 cases) who were postmenopausal at blood collection. For each biomarker, risk ratios (RRs) and 95% confidence intervals (CIs) for ER-positive breast cancer were estimated (1) per-doubling in biomarker concentration and (2) for quartiles of concentration with the lowest category as the reference, using weighted Poisson regression with a robust variance estimator.</p><p><strong>Results: </strong>The risk of postmenopausal ER-positive breast cancer increased per doubling in blood concentrations of leptin (RR: 1.13, 95% CI: 1.03, 1.25), adiponectin (RR: 1.10, 95% CI: 0.90, 1.34), tumour necrosis factor-alpha (RR: 1.27, 95% CI: 0.96, 1.68), and interleukin-10 (RR: 1.14, 95% CI: 1.01, 1.29). The RR for a doubling of the leptin-to-adiponectin ratio was 1.07 (0.99, 1.16). RRs for other biomarkers were 1.04 (0.93, 1.17) for interferon-gamma, 1.01 (0.88, 1.17) for interleukin-6, 0.98 (0.83, 1.16) for interleukin-8, and 1.03 (0.95, 1.11) for C-reactive protein.</p><p><strong>Conclusion: </strong>Systemic inflammation may be important in the risk of developing ER-positive breast cancer for postmenopausal females.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TSPAN32 enhances CAR-T cell potency by assembling IL-2 receptor complex and amplifying its intracellular signal transduction.","authors":"Yuanyuan Sun, Qiang Qiu, Bochuan Wang, Yunyu Feng, Jiaxin Wang, Cong Pan, Li Zheng, Huandi Qiu, Wei He, Zhiguang Su, Shaoguang Li, Yiguo Hu","doi":"10.1038/s41416-026-03592-x","DOIUrl":"https://doi.org/10.1038/s41416-026-03592-x","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor-engineered T cells (CAR-T) have shown substantial therapeutic potential in hematologic malignancies, but further improvement in T-cell functional capacity is needed to optimize efficacy. We observed reduced TSPAN32 expression in T cells from peripheral blood of patients with B-cell lymphoma. This study aimed to investigate whether TSPAN32 enhances CAR-T cell antitumor activity and to explore the underlying mechanism.</p><p><strong>Methods: </strong>TSPAN32 expression was assessed in T cells isolated from patients with B-cell lymphoma. T cells were engineered to co-express TSPAN32 and CD19-CAR, and their antitumor efficacy and cytokine secretion were evaluated in vitro and in subcutaneous tumor models in vivo. Gene expression profiling was performed to identify signaling pathways associated with TSPAN32 overexpression. Mechanistic studies examined the interaction between TSPAN32 and CD25 and its effect on IL-2 signaling. In addition, a transgenic mouse model with endogenous TSPAN32 overexpression and a TSPAN32-specific antibody (FF-37) were used to assess therapeutic potential.</p><p><strong>Results: </strong>TSPAN32 expression was reduced in T cells from B-cell lymphoma patients. Co-expression of TSPAN32 with CD19-CAR significantly enhanced antitumor activity and cytokine production compared with CD19-CAR alone in vitro. In vivo, T cells engineered with both CAR and TSPAN32 showed superior therapeutic efficacy in subcutaneous tumor models. Gene expression profiling indicated increased IL-2 signaling activation in TSPAN32-high CAR-T cells. Mechanistically, TSPAN32 interacted with CD25, promoting its aggregation on the T-cell surface and enhancing IL-2 signal transduction. Endogenous TSPAN32 overexpression in transgenic mice increased resistance to subcutaneous tumor growth. Furthermore, the TSPAN32-specific antibody FF-37 increased TSPAN32 expression and improved CAR-T antitumor efficacy.</p><p><strong>Conclusions: </strong>TSPAN32 enhances CAR-T cell antitumor function by promoting CD25 aggregation and IL-2 signaling activation. Increasing TSPAN32 expression, either through genetic engineering or the TSPAN32-specific antibody FF-37, may represent a promising strategy to improve CAR-T cell therapy.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PAX9 activates autophagy through a transcription-dependent mechanism, promoting EGFR degradation to restrict cell survival in oral cancer.","authors":"Chandra Sekhar Bhol, Rakesh Kumar Kar, Soumya Ranjan Mishra, Priyadarshini Mishra, Kewal Kumar Mahapatra, Xi Zhang, Samir Kumar Patra, Shankargouda Patil, Gautam Sethi, Daniel J Klionsky, Peter E Lobie, Vijay Pandey, Sujit Kumar Bhutia","doi":"10.1038/s41416-026-03608-6","DOIUrl":"10.1038/s41416-026-03608-6","url":null,"abstract":"<p><strong>Background: </strong>PAX9 (paired box 9) gene, a transcription factor belonging to the PAX family, is associated with craniofacial development. Dysregulation of PAX9 is associated with oral squamous cell carcinoma (OSCC), and its functional regulation in OSCC remains unknown.</p><p><strong>Methods: </strong>PAX9 expression was evaluated in human OSCC tissues and a DMBA-induced hamster oral carcinogenesis model, and its functional role in cell death and autophagy was assessed using PAX9 overexpression and PAX9 mutants in OSCC. Autophagy, lysosomal activity, apoptosis, EGFR degradation, and chemosensitivity were analysed in vitro and in an OSCC xenograft model.</p><p><strong>Results: </strong>Overexpression of PAX9 activated autophagy and enhanced lysosomal function through a transcription-dependent mechanism, thereby inducing apoptosis in OSCC. Mutations at L27P and I29T in PAX9 blocked autophagy and restored cell viability in OSCC. Interestingly, PAX9 was shown to activate lethal autophagy, which degrades EGFR, thereby inducing cell death and chemosensitisation in OSCC. Moreover, PAX9 expression decreased in higher-grade human oral cancers and in DMBA-induced hamster oral carcinogenesis, and in vitro exposure to carcinogens reduced PAX9 while increasing DNMT1, suggesting that DNA methylation may regulate PAX9 during oral carcinogenesis.</p><p><strong>Conclusion: </strong>PAX9 activates lethal autophagy, promoting EGFR degradation and apoptosis in OSCC, highlighting its tumour-suppressive potential and therapeutic relevance.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007675","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}