BJC reports最新文献

{"title":"Solid lipid nanoparticles in pancreatic cancer treatment.","authors":"Mia Dunn, Lewis Dymock, Clare Hoskins","doi":"10.1038/s44276-025-00130-9","DOIUrl":"https://doi.org/10.1038/s44276-025-00130-9","url":null,"abstract":"<p><p>Pancreatic cancer comes with one of the poorest prognoses of all cancers and as such it is crucial that new therapies are developed to improve on the current statistics. Currently, chemotherapy is the cornerstone of pancreatic cancer treatment with several drugs, and combinations of drugs being utilised for their anti-cancer effect. However, pancreatic cancer has a dense stroma around the tumour and intratumoral bacteria which result in drugs having difficulty penetrating the tumour or being metabolised by bacteria rendering them inactive. The utilisation of nanotechnology in chemotherapy for pancreatic cancer has been a huge area of focus for researchers worldwide with most of the focus being on lipid-based, inorganic and polymer-based nanoparticles. Solid lipid nanoparticles which have been studied since being first published in the 1990s, have been poorly researched for pancreatic cancer applications. Being composed of physiological lipids, solid lipid nanoparticles offer a greatly reduced risk of acute or chronic toxicities arising compared to inorganic or polymeric nanoparticles. They also possess the ability to improve on circulation time, permeability, and bioavailability of many first-line chemotherapeutics.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049995","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":"An aspirin a day keeps cancer at bay.","authors":"Mangesh A Thorat","doi":"10.1038/s44276-025-00138-1","DOIUrl":"https://doi.org/10.1038/s44276-025-00138-1","url":null,"abstract":"","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056956","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":"Immune checkpoint inhibitor therapy is associated with a decreased risk of developing melanoma brain metastases.","authors":"Anna Fager, Matilda Samuelsson, Roger Olofsson Bagge, Aldina Pivodic, Sara Bjursten, Max Levin, Henrik Jespersen, Lars Ny","doi":"10.1038/s44276-025-00137-2","DOIUrl":"https://doi.org/10.1038/s44276-025-00137-2","url":null,"abstract":"<p><strong>Background: </strong>Despite recent advancements in metastatic melanoma treatment, the emergence of melanoma brain metastases (MBM) continues to pose a challenge. This study aimed to explore factors associated with MBM development.</p><p><strong>Methods: </strong>This retrospective study included patients diagnosed with advanced melanoma (unresectable stages III and IV [M1a-c]) between 2013 and 2019 at Sahlgrenska University Hospital, Gothenburg, Sweden. Differences in baseline and primary tumor characteristics, mutational status, biomarker levels, and first-line treatment between patients who developed MBM (BM+) and patients who did not develop MBM (BM-) were analyzed using univariable and multivariable Cox proportional hazard regression.</p><p><strong>Result: </strong>Of 395 patients, 91 subsequently developed MBM. Patients who received immune checkpoint inhibitors (ICI) as first-line treatment had a reduced risk of MBM development (p ≤ 0.001). None of the eleven patients who received CTLA-4 inhibitors as monotherapy or in combination with PD-1 inhibitors as first-line treatment developed brain metastases. Elevated plasma levels of S100B (p = 0.021) and higher metastatic stage (p = 0.047) were also associated with an increased risk of MBM development.</p><p><strong>Conclusion: </strong>ICI treatment is associated with a decreased risk of MBM development, suggesting a protective role. Elevated S100B levels and stage IV disease at advanced melanoma diagnosis might indicate an increased risk of MBM development.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031980","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":"Increasing use of artificial intelligence in genomic medicine for cancer care- the promise and potential pitfalls.","authors":"Olivia O'Connor, Terri P McVeigh","doi":"10.1038/s44276-025-00135-4","DOIUrl":"10.1038/s44276-025-00135-4","url":null,"abstract":"<p><p>The field of genomic medicine produces large datasets, which need to be rapidly analysed to produce clinically actionable insights in cancer care. Artificial intelligence thrives on data, processing and learning from datasets with a degree of accuracy and efficiency that traditional computing algorithms can not achieve. Based on a patient's genome sequence, AI could allow earlier detection of cancer, inform personalised treatment plans and provide insights into prognostication. However, this valuable tool is met with skepticism, with stakeholders concerned over data security, liability for AI's mistakes due to hallucination and the threat to clinical jobs. This review highlights both the benefits and potential problems of using AI in genomic medicine for cancer care, with the aim to lessen the knowledge gap between clinicians and data scientists and facilitate the future deployment of AI in cancer care.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766142","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":"Tumour measurements on imaging for clinical trial: A national picture of service provision.","authors":"Georgina Hopkinson, Jonathan Taylor, Jonathan Wadsley, Angela Darekar, Christina Messiou, Dow-Mu Koh","doi":"10.1038/s44276-025-00131-8","DOIUrl":"10.1038/s44276-025-00131-8","url":null,"abstract":"<p><strong>Background: </strong>Radiological response evaluation metrics such as RECIST 1.1 inform critical endpoints in oncology trials. The UK was the 6th highest recruiter into oncology trials worldwide between 1999 and 2022, with almost 9000 oncology trials registered during the same period. However, the provision of tumour measurements for oncology trials is often ad hoc and patchy across the NHS. The aim of this work was to understand the barriers to providing an effective imaging tumour measurement service, gain insight into service delivery models and consider the successes and challenges from the perspective of both service providers and end users.</p><p><strong>Methods: </strong>An electronic survey was distributed to those who provide tumour measurement response review for clinical trials (service providers) and those that request and use such measurements in trial activities (service users).</p><p><strong>Results: </strong>Responses from 35 sites demonstrated substantial variation in service provision across the UK. Despite workforce pressures, service is largely delivered through radiologists with a minority utilising radiographer role extension. Only 20% of the service providers had dedicated training and 29% received robust financial reimbursement.</p><p><strong>Discussion: </strong>Service variation is likely a consequence of limited training, education and infrastructure to support robust service, compounded by increasing radiology workload and workforce pressures.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733691","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":"Germline copy number variants in RUNX1: An updated case report and a decade-old red herring.","authors":"Natalie T Deuitch, Amra Kajdic, Erica Bresciani, Marshall S Horwitz, Hamish S Scott, Katie Craft, Shawn Chong, David J Young, Lucy A Godley, Paul P Liu","doi":"10.1038/s44276-024-00117-y","DOIUrl":"10.1038/s44276-024-00117-y","url":null,"abstract":"<p><p>Pathogenic/likely pathogenic (P/LP) germline variants in RUNX1 cause familial platelet disorder with associated myeloid malignancies (FPDMM), also known as RUNX1-Familial Platelet Disorder (RUNX1-FPD, or FPD), a condition characterized by qualitative and quantitative platelet defects and predisposition to hematopoietic malignancies. Here, we present follow up to a case of a woman with acute myeloid leukemia and lifelong thrombocytopenia which had previously been attributed to presumptive pathogenic (P) GATA2 missense variants. However, re-evaluation with updated molecular technology sensitive for detection of copy number variants (CNVs) led to the identification of a P deletion of exons 5-6 in RUNX1, which had been undetected when examined at first presentation. This case highlights the importance of comprehensive molecular evaluation and careful variant interpretation, especially regarding CNVs.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733667","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":"A phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers.","authors":"Peter Gallagher, Christian Rolfo, Elena Elez, Julien Taieb, Jennifer Houlden, Linda Collins, Corran Roberts, Thierry André, Mark Lawler, Federica Di Nicolantonio, Margaret Grayson, Ruth Boyd, Vlad Popovici, Alberto Bardelli, Robbie Carson, Hajrah Khawaja, Pierre Laurent-Puig, Manuel Salto-Tellez, Bryan T Hennessy, Tim S Maughan, Josep Tabernero, Richard Adams, Robert Jones, Marc Peeters, Mark R Middleton, Richard H Wilson, Sandra Van Schaeybroeck","doi":"10.1038/s44276-025-00133-6","DOIUrl":"10.1038/s44276-025-00133-6","url":null,"abstract":"<p><strong>Background: </strong>Single-agent MEK1/2 inhibition has been disappointing in clinical trials targeting RAS mutant (MT) cancers, probably due to upstream receptor activation, resulting in resistance. We previously found that dual c-MET/MEK1/2 inhibition attenuated RASMT colorectal cancer (CRC) xenograft growth. In this study, we assessed safety of MEK1/2 inhibitor PD-0325901 with c-MET inhibitor crizotinib and determined the optimal biological doses for subsequent clinical trials.</p><p><strong>Methods: </strong>In this dose-escalation phase I trial, patients with advanced solid tumours received PD-0325901 with crizotinib, using a rolling-6 design to determine the maximum tolerable dose (MTD) and safety/tolerability. Blood samples for pharmacokinetics and skin biopsies were collected.</p><p><strong>Results: </strong>Twenty-five patients were recruited in 4 cohorts up to doses of crizotinib 200 mg B.D continuously with PD-0325901 8 mg B.D, days 1-21 every 28 days. One in six patients exhibited a dose-limiting toxicity at this dose level. Drug-related adverse events were in keeping with single-agent toxicity profiles. The best clinical response was stable disease in seven patients (29%).</p><p><strong>Conclusions: </strong>PD-0325901/crizotinib can be given together at pharmacologically-active doses. The MTD for PD-0325901/crizotinib was 8 mg B.D (days 1-21) and 200 mg B.D continuously in a 28-days cycle. The combination was further explored with an alternate MEK1/2 inhibitor in RASMT CRC patients.</p><p><strong>Eudract-number: </strong>2014-000463-40.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723085","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":"A novel multigene panel (Sig27) robustly predicts poor prognosis of renal cell carcinoma via high-level associations with immunosuppressive features.","authors":"Ying Dong, Bobby Shayegan, Yingying Su, Sandra Vega Neira, Damu Tang","doi":"10.1038/s44276-025-00128-3","DOIUrl":"10.1038/s44276-025-00128-3","url":null,"abstract":"<p><strong>Background: </strong>We investigated a 27-gene panel (Sig27), derived from prostate cancer, for risk stratification of RCC (clear cell RCC/ccRCC, papillary RCC/pRCC, and chromophobe RCC/chRCC).</p><p><strong>Methods: </strong>Sig27 gene expressions were examined in 960 RCC and 201 kidney tissues. Sig27 was evaluated for predicting overall survival (OS), association with immune checkpoints (IC), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC), and tumor-associated macrophages (TAM) in RCC.</p><p><strong>Results: </strong>Sig27 robustly predicts OS of ccRCC, pRCC, and chRCC. Sig27 stratifies high-risk ccRCCs: median survival month (MSM) 19.3 and 80.4% of deaths and high-risk pRCCs (MSM 19.6 and 58.6% of death) compared to low-risk ccRCCs (2.9% of death) and pRCCs (2.7% of fatality). Sig27 contains several novel genes related to the RCC immunosuppressive features. FPR3, NOD2, MCTP1, LAMP3, TFEC, and FAM65B are highly correlated with MDSC, Treg, TAM and multiple (≥12) ICs in RCCs. FPR3 and NOD2 are pattern recognition receptors and initiate proinflammatory responses via sensing pathogen-associated molecular patterns and damage-associated molecular patterns; their upregulations may contribute to chronic inflammation in RCC. The Sig27 metagene is expressed in ccRCC-associated immune cells: exhausted CD8T cells, TAM, Treg, and others.</p><p><strong>Conclusions: </strong>Sig27 is a novel and effective pan-RCC biomarker with high-level associations with RCC immunosuppressive features.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652957","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":"Epidemiology of multimorbidity in childhood cancer survivors: a matched cohort study of inpatient hospitalisations in Western Australia.","authors":"Tasnim Abdalla, Jeneva L Ohan, Angela Ives, Daniel White, Catherine S Choong, Max Bulsara, Jason D Pole","doi":"10.1038/s44276-024-00114-1","DOIUrl":"10.1038/s44276-024-00114-1","url":null,"abstract":"<p><strong>Background: </strong>Childhood cancer survivors (CCS) experience an elevated burden of health complications, underscoring the importance of understanding the patterns of multimorbidity to guide the management of survivors with complex medical needs.</p><p><strong>Methods: </strong>We examined the patterns of hospitalisations with multimorbidity in 5-year CCS (n = 2938) and age- and sex-matched non-cancer comparisons (n = 24,792) using statewide records of inpatient admissions in Western Australia from 1987 to 2019.</p><p><strong>Results: </strong>Multimorbidity rates were higher for CCS (10.6, 95%CI 10.2-10.9) than for non-cancer comparisons (3.2, 95%CI 3.2-3.3). CCS exhibited a significantly higher adjusted hazard ratio of multimorbidity, particularly when admitted for neoplasms (14.6, 95%CI 11.2-19.1), as well as blood (7.3, 95%CI 4.9-10.7), neurological and sensory (5.2, 95%CI 4.2-6.6), and cardiovascular (3.6, 95%CI 2.6-4.8) diseases. By the age of 55 years, chronic multimorbidity was more prevalent in survivors than in comparisons (14.5% vs. 5.3%). Psychiatric disorders were common comorbidities, particularly in those admitted for neurological and sensory (71.1%), endocrine (61.5%), and digestive (59.3%) diseases. Multimorbidity during hospitalisation increased the length of hospital stay (p < 0.05). Key condition clusters included (1) psychoactive substance  dependence, alcohol misuse, and other mental disorders; (2) hypertension, diabetes, kidney disease, and musculoskeletal diseases; (3) epilepsy, hypothyroidism, and other liver diseases; and (4) hypertension, kidney disease, and other liver diseases.</p><p><strong>Conclusions: </strong>These findings suggest that exposure to cancer in childhood elevates the risk of multimorbidity. The reconfiguration of healthcare delivery to enhance personalised care and clinical integration is essential for effectively managing multimorbidity in this population.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627069","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":"Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic review.","authors":"Ying-Wen Wang, Isaac Allen, Gabriel Funingana, Marc Tischkowitz, Yvonne Walburga Joko-Fru","doi":"10.1038/s44276-025-00122-9","DOIUrl":"10.1038/s44276-025-00122-9","url":null,"abstract":"<p><strong>Background: </strong>PARP inhibitors are effective in treating ovarian cancer, especially for BRCA1/2 pathogenic variant carriers and those with HRD (homologous recombination deficiency). Concerns over toxicity and costs have led to the search for predictive biomarkers. We present an updated systematic review, expanding on a previous ESMO review on PARP inhibitor biomarkers.</p><p><strong>Methods: </strong>Following ESMO's 2020 review protocol, we extended our search to March 31, 2023, including PubMed and clinical trial data. We also reviewed the reference lists of review articles. We conducted a meta-analysis using a random-effects model to evaluate hazard ratios and assess the predictive potential of biomarkers and the effectiveness of PARP inhibitors in survival.</p><p><strong>Results: </strong>We found 375 articles, 103 of which were included after screening (62 primary research, 41 reviews). HRD remained the primary biomarker (95%), particularly BRCA1/2 variants (77%). In the non-HRD category, six articles (10%) introduced innovative biomarkers, including ADP-ribosylation, HOXA9 promoter methylation, patient-derived organoids, KELIM, and SLFN11.</p><p><strong>Discussion: </strong>Prospective assessment of real-time homologous recombination repair via nuclear RAD51 levels shows promise but needs validation. Emerging biomarkers like ADP-ribosylation, HOXA9 promoter methylation, patient-derived organoids, KELIM, and SLFN11 offer potential but require large-scale validation.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607742","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}