BMJ oncology最新文献

{"title":"Osteoclast-expanded supercharged NK cells perform superior antitumour effector functions.","authors":"Meng-Wei Ko, Ao Mei, Emanuela Senjor, Milica Perišić Nanut, Lucy Wanrong Gao, Paul Wong, Po-Chun Chen, Whitaker Cohn, Julian P Whitelegge, Janko Kos, Kawaljit Kaur, Subramaniam Malarkannan, Anahid Jewett","doi":"10.1136/bmjonc-2024-000676","DOIUrl":"10.1136/bmjonc-2024-000676","url":null,"abstract":"<p><strong>Objective: </strong>Natural killer (NK) cells are the largest innate lymphocyte subset with potent antitumour and antiviral functions. However, clinical utilisation of human NK cells is hampered due to a lack of reliable methods to augment their antitumour potential. We demonstrated technology in which human NK cells were cocultured with osteoclasts in the presence of probiotic bacteria. This approach significantly augmented the antitumour cytotoxicity and polyfunctionality of human NK cells, resulting in the generation of supercharged NK (sNK) cells.</p><p><strong>Methods and analysis: </strong>We explored the proteomic, transcriptomic and functional characterisation of sNK cells using cell imaging, flow cytometric analysis, 51-chromium release cytotoxicity assay, ELISA, ELIspot, IsoPLexis single-cell secretome analysis, proteomic analysis, RNA analysis, western blot and enzyme kinetics.</p><p><strong>Results: </strong>We found that sNK cells were less susceptible to split anergy and tumour-induced exhaustion. Proteomic analyses revealed that sNK cells significantly increased their cell motility and proliferation. Single-cell transcriptomes uncovered sNK cells undertaking a unique differentiation trajectory and turning on STAT1, JUN, BHLHE40, ELF1, MAX and MYC regulons essential for augmenting antitumour effector functions and proliferation, respectively. Both proteomic and single-cell transcriptomes revealed that an increase in Cathepsin C helped to augment the quantity and function of Granzyme B.</p><p><strong>Conclusions: </strong>These results support that this unique method produces potent NK cells for clinical utilisation and delineate the molecular mechanisms associated with this process.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000676"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the gap between guidelines and practice in Lynch syndrome screening for endometrial cancer.","authors":"Hiroshi Yoshida","doi":"10.1136/bmjonc-2025-000821","DOIUrl":"10.1136/bmjonc-2025-000821","url":null,"abstract":"","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000821"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mismatch in testing: a retrospective analysis of mismatch repair testing in endometrial cancer and Lynch syndrome diagnosis in multiple specialist centres in the UK and Ireland (March 2022-March 2023).","authors":"Neil Ryan, Kane Alexander Lennie, Adam Naskretski, Craig Anderson, Lorena Mihaita, Sanduni Abeysuriya, Maria Ashworth, Victoria Cullimore, Lucy Dobson, Nathan Graham, Radha Graham, Shaun Haran, Zuzanna Holwek, Ashton Hunt, Ben Johnston, Rebecca Karkia, Georgios Kouklidis, Elaine Leung, Aiste McCormick, Josh McMullan, Aileen Mohan, Alison Montgomery, Claire Newton, Manolis Nikolopoulos, Catriona Norden, Charlotte Nott, Gemma Owens, Phillip Rolland, Sammuel Ricketts, Vanitha Sivalingam, David Smith, Freweini Tesfai, Laura Tookman, Chenai Whacha, Peter Sanderson","doi":"10.1136/bmjonc-2024-000688","DOIUrl":"10.1136/bmjonc-2024-000688","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the implementation of Lynch syndrome testing in endometrial cancer (EC) across the UK and Ireland, identify diagnostic gaps and evaluate adherence to the National Institute for Health and Care Excellence (NICE) guidelines recommending routine mismatch repair (MMR) deficiency testing.</p><p><strong>Methods and analysis: </strong>A multi-centre, cross-sectional retrospective study conducted in line with STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Secondary care cancer centres across the UK and Republic of Ireland were identified with support from the ARGO (Audit and Research in Gynaecological Oncology) Collaborative and invited to complete a bespoke data collection tool.</p><p><strong>Results: </strong>Data from 2716 histologically confirmed EC cases treated between March 2022 and March 2023 were collected. After excluding misdiagnosed and inconsistent cases, 2549 were analysed. The cohort had a mean age of 66.3 years and a mean body mass index of 33.43 kg/m²; 69.3% had endometrioid EC histology. MMR testing was performed in 91% of cases, with 27.6% classified as MMR deficient, mainly due to MLH1/PMS2 loss (77.4%). Of the 510 cases requiring hypermethylation analysis, results were missing for 62. Of the 181 participants eligible for genetic counselling, 64% were referred and 48% underwent germline testing, identifying 19 new Lynch syndrome cases. MMR-deficient tumours were diagnosed at earlier stages and lower grades compared with MMR-proficient tumours.</p><p><strong>Conclusions: </strong>While tumour based MMR testing is widely performed, diagnostic attrition significantly impairs the pathway to definitive Lynch syndrome diagnosis. Addressing barriers to genetic counselling and germline testing is crucial for improving patient outcomes and the cost-effectiveness of Lynch syndrome screening.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000688"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of protein biomarker candidates associated with organ-specific immune-related toxicity and response to management by plasma proteomics.","authors":"Anders Handrup Kverneland, Ole Østergaard, Joel Emanuel Sohlin, Inge Mansfield Noringriis, Rebecca S Jurlander, Jesper Velgaard Olsen, Inge Marie Svane","doi":"10.1136/bmjonc-2024-000696","DOIUrl":"10.1136/bmjonc-2024-000696","url":null,"abstract":"<p><strong>Objective: </strong>Immune-related adverse events (irAEs) are a growing challenge with checkpoint inhibitors (CPIs) and are complicated by the lack of suitable response biomarkers in many irAEs. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based proteomics is a system-wide unbiased analysis method suited for biomarker discovery. In this study, plasma samples from patients suffering from irAEs were analysed using MS-based proteomics.</p><p><strong>Methods and analysis: </strong>The discovery cohort consisted of 37 melanoma patients experiencing an irAE (colitis, hepatitis and nephritis) collected around irAE management. The validation cohort consisted of 34 irAE patients (colitis, hepatitis, nephritis and pneumonitis) at management, with a control group consisting of 34 patients treated with CPIs without an irAE. The plasma samples were processed with bottom-up proteomics and analysed on an Orbitrap Astral Mass Spectrometer with short LC gradients.</p><p><strong>Results: </strong>During an irAE, we found upregulation of multiple acute-phase protein reactants. The level of these was higher in patients in combination CPI therapy-also observed in the control cohort without irAE. We found multiple hepatic proteins associated with immune-related hepatitis, including fructose-biphosphate aldolase B (ALDOB), showing the widest dynamic range. Further, we found a correlation of lipocalin-2/neutrophil gelatinase-associated lipocalin (LCN2/NGAL) to nephritis and colitis with a significant correlation to the clinical toxicity grade confirmed by an immunoassay. Finally, high levels of angiotensinogen (AGT), chitinase-3-like protein 1 (CHI3L1) and lectin mannose-binding 2 (LMAN2) showed a significant association with poor prednisolone response.</p><p><strong>Conclusion: </strong>In conclusion, using LC-MS/MS-based plasma proteomics, we identified several irAE-related biomarker candidates to be further assessed for toxicity grading and management in the context of monitoring irAEs.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000696"},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conclusion about colorectal cancer incidence in people who smoke.","authors":"Rodney J Scott","doi":"10.1136/bmjonc-2025-000855","DOIUrl":"10.1136/bmjonc-2025-000855","url":null,"abstract":"","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000855"},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smoking habit and long-term colorectal cancer incidence by exome-wide mutational and neoantigen loads: evidence based on the prospective cohort incident-tumour biobank method.","authors":"Tsuyoshi Hamada, Tomotaka Ugai, Carino Gurjao, Satoko Ugai, Xuehong Zhang, Koichiro Haruki, Yasutoshi Takashima, Naohiko Akimoto, Mai Chan Lau, Kosuke Matsuda, Nobuhiro Nakazawa, Mayu Higashioka, Satoshi Miyahara, Keisuke Kosumi, Yohei Masugi, Li Liu, Yin Cao, Daniel Nevo, Molin Wang, Reiko Nishihara, Sachet A Shukla, Catherine J Wu, Levi A Garraway, Jeffrey A Meyerhardt, Edward L Giovannucci, Jonathan A Nowak, Charles S Fuchs, Andrew T Chan, Mingyang Song, Marios Giannakis, Shuji Ogino","doi":"10.1136/bmjonc-2025-000787","DOIUrl":"10.1136/bmjonc-2025-000787","url":null,"abstract":"<p><strong>Objective: </strong>To test the hypothesis that the association of smoking with long-term colorectal cancer incidence may be stronger for tumours with higher mutational and neoantigen loads.</p><p><strong>Methods and analysis: </strong>In the Nurses' Health Study (1980-2012) and the Health Professionals Follow-up Study (1986-2012), our novel prospective cohort incident-tumour biobank method (PCIBM) used 3053 incident colorectal carcinoma cases including 752 cases with whole-exome sequencing data. Using the multivariable duplication-method Cox regression model with the inverse probability weighting to adjust for the selection bias due to tissue availability, we assessed a differential association of cigarette smoking with colorectal carcinoma incidence by an exome-wide tumour mutational burden (e-TMB) or neoantigen load.</p><p><strong>Results: </strong>The association of pack-years smoked with colorectal cancer incidence differed by e-TMB (P_{heterogeneity}<0.001). Multivariable-adjusted HRs for e-TMB-high (≥10 mutations/megabase) tumours were 1.28 (95% CI 0.72 to 2.28) and 2.56 (95% CI 1.61 to 4.07) for 1-19 and ≥20 pack-years (vs 0 pack-years; P_trend<0.001), respectively. In contrast, pack-years smoked were not associated with e-TMB-low tumour incidence (P_trend=0.67). A similar differential association was observed for the neoantigen load (P_{heterogeneity}=0.017). The differential association by e-TMB appeared consistent in the strata of CpG island methylator phenotype status, <i>BRAF</i> mutation or lymphocytic infiltrates.</p><p><strong>Conclusions: </strong>Smoking is more strongly associated with the long-term incidence of colorectal carcinoma harbouring higher mutational and neoantigen loads. Our PCIBM-based evidence supports the immunosuppressive effect of smoking and the potential of smoking cessation in improving antitumour immunity for cancer prevention and treatment.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000787"},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specificity of Food and Drug Administration postmarketing requirements and associations with timely submissions and regulatory decisions for oncology accelerated approvals, 2011-2023: a cross-sectional analysis.","authors":"Martin Kurian, William J Ferrell, Ernesto Ulloa Perez, Rebecca Hubbard, Steven Joffe, Ronac Mamtani, Ravi B Parikh, Holly Fernandez Lynch","doi":"10.1136/bmjonc-2024-000659","DOIUrl":"10.1136/bmjonc-2024-000659","url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Objectives: </strong>To assess the specificity of postmarketing requirement (PMR) statements and associations between PMR statement specificity and PMR study characteristics, timeliness and regulatory decisions.</p><p><strong>Methods and analysis: </strong>This was a cross-sectional analysis of publicly available Food and Drug Administration (FDA) databases to characterise PMR statements for oncology accelerated approvals (AAs) between January 2011 and July 2023. Characteristics of trials supporting AA and PMR studies were identified from product labels on the Drugs@FDA database and ClinicalTrials.gov. Main outcomes and measures included PMR statement characteristics, PMR study submission timeliness (on-time vs late) and regulatory decision (regular approval vs withdrawal).</p><p><strong>Results: </strong>We analysed 181 PMR statements for 161 oncology indications. Most PMR statements specified target population (98%), endpoints (81% (44% included clinical endpoints; 37% surrogate endpoints only)), use of randomisation (63%) and comparator (54%). Fewer PMR statements specified a particular trial or protocol (45%), follow-up duration (30%), enrolment targets (26%), multicentre trial (24%), double-blinding (13%) or enrolment diversity (8%). PMR statements for indications granted regular approval were more likely than those for withdrawn indications to specify follow-up duration <1 year (27% vs 0%, p<0.001), allow endpoints other than overall or progression-free survival (27% vs 4%, p=0.01) and mention a specific trial or protocol (71% vs 36%, p=0.003). Compared to those submitted late, on-time PMR studies had fewer sites (110 vs 156, p=0.03), less use of blinding (20% vs 42%, p=0.02), more use of a continuous trial for AA and PMR (37% vs 8%, p=0.003) and more use of primary endpoints other than overall or progression-free survival (37% vs 6%, p<0.001).</p><p><strong>Conclusion: </strong>PMR statement specificity for oncology AAs varies substantially. Less rigorous PMR statement and study characteristics were associated with timely PMR study submission and transition to regular approval but with important trade-offs. Given that AAs are granted without demonstrated clinical benefit, improving the balance between PMR study timeliness and rigour should be a priority when negotiating PMR statements.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000659"},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large language models in oncology: a review.","authors":"David Chen, Rod Parsa, Karl Swanson, John-Jose Nunez, Andrew Critch, Danielle S Bitterman, Fei-Fei Liu, Srinivas Raman","doi":"10.1136/bmjonc-2025-000759","DOIUrl":"10.1136/bmjonc-2025-000759","url":null,"abstract":"<p><p>Large language models (LLMs) have demonstrated emergent human-like capabilities in natural language processing, leading to enthusiasm about their integration in healthcare environments. In oncology, where synthesising complex, multimodal data is essential, LLMs offer a promising avenue for supporting clinical decision-making, enhancing patient care, and accelerating research. This narrative review aims to highlight the current state of LLMs in medicine; applications of LLMs in oncology for clinicians, patients, and translational research; and future research directions. Clinician-facing LLMs enable clinical decision support and enable automated data extraction from electronic health records and literature to inform decision-making. Patient-facing LLMs offer the potential for disseminating accessible cancer information and psychosocial support. However, LLMs face limitations that must be addressed before clinical adoption, including risks of hallucinations, poor generalisation, ethical concerns, and scope integration. We propose the incorporation of LLMs within compound artificial intelligence systems to facilitate adoption and efficiency in oncology. This narrative review serves as a non-technical primer for clinicians to understand, evaluate, and participate as active users who can inform the design and iterative improvement of LLM technologies deployed in oncology settings. While LLMs are not intended to replace oncologists, they can serve as powerful tools to augment clinical expertise and patient-centred care, reinforcing their role as a valuable adjunct in the evolving landscape of oncology.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000759"},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ending nuclear weapons, before they end us.","authors":"Chris Zielinski","doi":"10.1136/bmjonc-2025-000853","DOIUrl":"10.1136/bmjonc-2025-000853","url":null,"abstract":"","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000853"},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Prospective evaluation of artificial intelligence (AI) applications for use in cancer pathways following diagnosis: a systematic review.","authors":"","doi":"10.1136/bmjonc-2023-000255corr1","DOIUrl":"https://doi.org/10.1136/bmjonc-2023-000255corr1","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1136/bmjonc-2023-000255.].</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"4 1","pages":"e000255corr1"},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}