Pharmacogenomics Journal最新文献

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Benchmarking large language models for replication of guideline-based PGx recommendations. 对大型语言模型进行基准测试,以复制基于指南的PGx建议。
IF 2.9 3区 医学
Pharmacogenomics Journal Pub Date : 2025-07-26 DOI: 10.1038/s41397-025-00383-0
Mike Zack, Ioan Slobodchikov, Danil Stupichev, Alex Moore, David Sokolov, Igor Trifonov, Allan Gobbs
{"title":"Benchmarking large language models for replication of guideline-based PGx recommendations.","authors":"Mike Zack, Ioan Slobodchikov, Danil Stupichev, Alex Moore, David Sokolov, Igor Trifonov, Allan Gobbs","doi":"10.1038/s41397-025-00383-0","DOIUrl":"https://doi.org/10.1038/s41397-025-00383-0","url":null,"abstract":"<p><p>We evaluated the ability of large language models (LLMs) to generate clinically accurate pharmacogenomic (PGx) recommendations aligned with CPIC guidelines. Using a benchmark of 599 curated gene-drug-phenotype scenarios, we compared five leading models, including GPT-4o and fine-tuned LLaMA variants, through both standard lexical metrics and a novel semantic evaluation framework (LLM Score) validated by expert review. General-purpose models frequently produced incomplete or unsafe outputs, while our domain-adapted model achieved superior performance, with an LLM Score of 0.92 and significantly faster inference speed. Results highlight the importance of fine-tuning and structured prompting over model scale alone. This work establishes a robust framework for evaluating PGx-specific LLMs and demonstrates the feasibility of safer, AI-driven personalized medicine.</p>","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"25 4","pages":"23"},"PeriodicalIF":2.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Impact of low BMI and ABCC2 genotype on the clinical response of sequential anthracycline-taxane chemotherapy receiving breast cancer patients: a hospital-based study. 低BMI和ABCC2基因型对序贯蒽环类-紫杉烷化疗乳腺癌患者临床疗效的影响:一项基于医院的研究
IF 2.9 3区 医学
Pharmacogenomics Journal Pub Date : 2025-07-16 DOI: 10.1038/s41397-025-00380-3
Tanuma Mistry, Sanghamitra Sengupta, R Suresh Kumar, Nisha Thakur, Partha Nath, Neyaz Alam, Vilas D Nasare
{"title":"Impact of low BMI and ABCC2 genotype on the clinical response of sequential anthracycline-taxane chemotherapy receiving breast cancer patients: a hospital-based study.","authors":"Tanuma Mistry, Sanghamitra Sengupta, R Suresh Kumar, Nisha Thakur, Partha Nath, Neyaz Alam, Vilas D Nasare","doi":"10.1038/s41397-025-00380-3","DOIUrl":"https://doi.org/10.1038/s41397-025-00380-3","url":null,"abstract":"<p><p>This study investigates combine effect of low BMI and possible pharmacogenetic influence of ABC gene polymorphisms in treatment responses of BC patients. BMI was analysed prior to commencement of chemotherapy. Clinical response was evaluated by radiological imaging and categorised as per RECISTv.1 criteria. SNPs (C1236T, C3435T, C58626A) in ABCB1 and ABCC2 gene were selected. 148 patients were analysed using PCR-RFLP. ABCC2 (58626AA) was significantly associated with treatment non-responsiveness in all genetic models namely dominant (OR 2.954; [1.442-6.051]; p = 0.003), recessive (OR 5.723; [2.48-13.20]; p < 0.0001), codominant (χ<sup>2</sup> 21.219; p < 0.0001). The proportion of ORR and NRs were significantly different between low (<18.5) and high (≥18.5) BMI classes (OR 16.097; [7.12-36.35]; p < 0.0001). Furthermore, when treatment response was combined with BMI groups, significant associations were observed for C58626A SNP across all genetic models among low BMI group: dominant (OR 3.324; [1.012-10.406]; p = 0.041), recessive (OR 7.250; [1.533-34.278]; p = 0.012) and codominant (χ<sup>2</sup> 8.657; p = 0.013). Both PFS (35.31 months; p = 0.005) and OS (39.75 months; p = 0.032) were lowered among AA genotype (ABCC2) while the hazard risk of this genotype was further increased in low BMI patients (HR 1.963). 3435CT genotypes in ABCB1 gene showed 87% reduction in risk of death (HR 0.13; p = 0.025). Low BMI independently and jointly with 58626AA genotype of ABCC2 gene was responsible for poor chemotherapy response and survival outcome among AC-T regimen receiving BC patients. Together, this study underscores the importance of genetic counselling and nutritional assessment for favourable treatment outcomes.</p>","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"25 4","pages":"22"},"PeriodicalIF":2.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Correction: Integrating rare genetic variants into DPYD pharmacogenetic testing may help preventing fluoropyrimidine-induced toxicity. 更正:将罕见的遗传变异纳入DPYD药理学检测可能有助于预防氟嘧啶引起的毒性。
IF 2.9 3区 医学
Pharmacogenomics Journal Pub Date : 2025-07-15 DOI: 10.1038/s41397-025-00381-2
Romain Larrue, Sandy Fellah, Benjamin Hennart, Naoual Sabaouni, Nihad Boukrout, Cynthia Van der Hauwaert, Clément Delage, Meyling Cheok, Michaël Perrais, Christelle Cauffiez, Delphine Allorge, Nicolas Pottier
{"title":"Correction: Integrating rare genetic variants into DPYD pharmacogenetic testing may help preventing fluoropyrimidine-induced toxicity.","authors":"Romain Larrue, Sandy Fellah, Benjamin Hennart, Naoual Sabaouni, Nihad Boukrout, Cynthia Van der Hauwaert, Clément Delage, Meyling Cheok, Michaël Perrais, Christelle Cauffiez, Delphine Allorge, Nicolas Pottier","doi":"10.1038/s41397-025-00381-2","DOIUrl":"10.1038/s41397-025-00381-2","url":null,"abstract":"","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"25 4","pages":"21"},"PeriodicalIF":2.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacogenomic-guided opioid therapy for pain: a systematic review and meta-analysis of randomised controlled trials. 药物基因组学指导的阿片类药物治疗疼痛:随机对照试验的系统回顾和荟萃分析。
IF 2.9 3区 医学
Pharmacogenomics Journal Pub Date : 2025-07-12 DOI: 10.1038/s41397-025-00379-w
S Jethwa, M Ball, K Langlands
{"title":"Pharmacogenomic-guided opioid therapy for pain: a systematic review and meta-analysis of randomised controlled trials.","authors":"S Jethwa, M Ball, K Langlands","doi":"10.1038/s41397-025-00379-w","DOIUrl":"10.1038/s41397-025-00379-w","url":null,"abstract":"<p><p>Optimising opioid therapy is challenging due to variable patient responses linked to genetic variation. Pharmacogenomic-guided prescribing holds promise for personalisation, but its clinical effectiveness requires evaluation. We performed a systematic review and meta-analysis of RCTs comparing pharmacogenomic-guided versus standard opioid prescribing in adults. Adhering to PRISMA, we assessed risk of bias (RoB 2) and evidence certainty (GRADE). Six RCTs met inclusion criteria from 2496 screened articles. Meta-analysis showed pharmacogenomic-guided prescribing was associated with significantly reduced opioid consumption (SMD -0.38, 95% CI -0.67 to -0.08, p = 0.01). However, no significant difference in pain intensity was observed between groups (SMD -0.31, 95% CI -0.89 to 0.27, p = 0.30). Evidence regarding adverse events was limited to one trial, which reported a statistically significant reduction in incidence in the pharmacogenomic group (median [IQR]: 1 [0-2] vs. 3 [1-5]; p < 0.01). Further research is needed to determine if pharmacogenomics can improve opioid therapy outcomes.</p>","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"25 4","pages":"20"},"PeriodicalIF":2.9,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Utilisation of drugs with pharmacogenetic recommendations in children in Switzerland. 瑞士儿童药物遗传学建议用药情况。
IF 2.9 3区 医学
Pharmacogenomics Journal Pub Date : 2025-07-11 DOI: 10.1038/s41397-025-00378-x
Nina L Wittwer, Christoph R Meier, Carola A Huber, Romy Tilen, Canan Yilmaz, Henriette E Meyer Zu Schwabedissen, Samuel Allemann, Cornelia Schneider
{"title":"Utilisation of drugs with pharmacogenetic recommendations in children in Switzerland.","authors":"Nina L Wittwer, Christoph R Meier, Carola A Huber, Romy Tilen, Canan Yilmaz, Henriette E Meyer Zu Schwabedissen, Samuel Allemann, Cornelia Schneider","doi":"10.1038/s41397-025-00378-x","DOIUrl":"10.1038/s41397-025-00378-x","url":null,"abstract":"<p><p>Pharmacogenetics (PGx) is increasingly implemented in the adult population, but its potential in children remains uncertain. The aim of this study was to investigate PGx drug utilization in children in Switzerland, using Helsana claims data between 2017 and 2021. We identified 82 drugs with paediatric guideline annotations associated with variants in 24 genes from the Pharmacogenomics Knowledgebase. Of 159 172 children continuously insured, 66.1% claimed at least one PGx drug during the study period. The three PGx drugs with the highest user numbers were systemically administered ibuprofen (59.1%), ondansetron (8.3%), and locally administered fluorouracil (7.5%). Over 96% of all potential drug-gene interactions were caused by seven genes (CYP2C9, CYP2D6, DPYD, CYP2C19, MT-RNR1, CACNA1S, and RYR1). The high number of children claiming PGx drugs in Switzerland implies that a significant number of children could benefit from PGx testing.</p>","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"25 4","pages":"19"},"PeriodicalIF":2.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analyzing pharmacogenetics cost effectiveness and savings across common health conditions in the United States. 分析美国常见健康状况的药物遗传学成本效益和节省。
IF 2.9 3区 医学
Pharmacogenomics Journal Pub Date : 2025-07-08 DOI: 10.1038/s41397-025-00376-z
Mayuri S Patel, Emily J Cicali, Frank A Orlando
{"title":"Analyzing pharmacogenetics cost effectiveness and savings across common health conditions in the United States.","authors":"Mayuri S Patel, Emily J Cicali, Frank A Orlando","doi":"10.1038/s41397-025-00376-z","DOIUrl":"https://doi.org/10.1038/s41397-025-00376-z","url":null,"abstract":"<p><p>This review describes healthcare cost effectiveness/savings for pharmacogenetics (PGx) and relevant clinical outcomes in selected common health conditions. PGx allows targeted drug treatment based on genotype and phenotype. Studies highlight how PGx testing reduces the morbidity and mortality of adverse drug reactions (ADRs) by predicting unexpected drug metabolism due to genetic variation in cytochrome P450 enzymes (CYPs) and drug-drug interactions caused by altered CYP enzyme phenotype. Despite many available PGx testing platforms and PGx-guided treatments, clinical implementation remains challenging and slow due to limited (1) insurance coverage and reimbursement of testing and pharmacist interpretation, (2) outcome data such as evidence showing the benefits of preemptive PGx testing for efficacy or ADR prevention, and (3) promotion of PGx testing among healthcare professionals. Of these, cost is the most significant barrier to patients and the healthcare system. This review describes how PGx testing can be cost effective or cost saving for payors and the healthcare system, especially for depression, cardiovascular disease, and ADRs.</p>","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"25 4","pages":"18"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
STRIPE partners in precision medicine: laboratory perspective. 精准医疗领域的STRIPE合作伙伴:实验室视角。
IF 2.9 3区 医学
Pharmacogenomics Journal Pub Date : 2025-06-30 DOI: 10.1038/s41397-025-00377-y
Ben L Kong, Benjamin G Brown, Victoria M Pratt, Bronwyn Ramey, J Shawn Jones, Sara L Rogers
{"title":"STRIPE partners in precision medicine: laboratory perspective.","authors":"Ben L Kong, Benjamin G Brown, Victoria M Pratt, Bronwyn Ramey, J Shawn Jones, Sara L Rogers","doi":"10.1038/s41397-025-00377-y","DOIUrl":"https://doi.org/10.1038/s41397-025-00377-y","url":null,"abstract":"","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"25 4","pages":"17"},"PeriodicalIF":2.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
CYP2C19 point-of-care testing: where are we now and where should we go? CYP2C19即时检测:我们现在在哪里,我们应该去哪里?
IF 2.9 3区 医学
Pharmacogenomics Journal Pub Date : 2025-06-13 DOI: 10.1038/s41397-025-00375-0
Leticia A Shea
{"title":"CYP2C19 point-of-care testing: where are we now and where should we go?","authors":"Leticia A Shea","doi":"10.1038/s41397-025-00375-0","DOIUrl":"https://doi.org/10.1038/s41397-025-00375-0","url":null,"abstract":"","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"25 4","pages":"16"},"PeriodicalIF":2.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Influence of genetic biomarkers on cardiac diseases in childhood cancer survivors: a systematic review. 遗传生物标志物对儿童癌症幸存者心脏疾病的影响:系统综述
IF 2.9 3区 医学
Pharmacogenomics Journal Pub Date : 2025-05-24 DOI: 10.1038/s41397-025-00369-y
Naïla Aba, Claire Ducos, Eric Morel, Chiraz El Fayech, Brice Fresneau, Florent de Vathaire, Gwénaël Le Teuff, Nadia Haddy
{"title":"Influence of genetic biomarkers on cardiac diseases in childhood cancer survivors: a systematic review.","authors":"Naïla Aba, Claire Ducos, Eric Morel, Chiraz El Fayech, Brice Fresneau, Florent de Vathaire, Gwénaël Le Teuff, Nadia Haddy","doi":"10.1038/s41397-025-00369-y","DOIUrl":"10.1038/s41397-025-00369-y","url":null,"abstract":"<p><p>Childhood cancer survivors (CCS) often suffer from cardiac disease (CD) after treatment that included anthracycline and radiotherapy involving the heart. However, the variability in CD occurrence cannot be explained solely by these treatments, suggesting the existence of genetic predisposition. We conducted a systematic review searching on Medline-PubMed and Scopus, to identify studies reporting associations between genetic factors and CD in CCS. We included studies published up to 11 April 2023, with no lower limit, and assessed the quality of genetic associations by the Q-genie tool. As a result, 20 studies were included (15 case-control and five cohorts), revealing several genes and variants associated with cardiomyopathy, among which, SLC28A3-rs7853758, RARG-rs2229774, P2RX7-rs208294 and P2RX7-rs3751143 variants gave the most consistent findings. This review highlights the necessity to establish a set of clinically useful genes and variants to identify patients most at risk of developing cardiomyopathy, and to implement monitoring and prevention strategies.</p>","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"25 3","pages":"15"},"PeriodicalIF":2.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
KHSRP promotes the malignant behavior and cisplatin resistance of bladder cancer cells through the CLASP2/MAPRE1 axis. KHSRP通过CLASP2/MAPRE1轴促进膀胱癌细胞的恶性行为和顺铂耐药。
IF 2.9 3区 医学
Pharmacogenomics Journal Pub Date : 2025-05-17 DOI: 10.1038/s41397-025-00374-1
Ruizhe Wang, Cheng Zhao, Zhenyu Ou, Lingxiao Chen
{"title":"KHSRP promotes the malignant behavior and cisplatin resistance of bladder cancer cells through the CLASP2/MAPRE1 axis.","authors":"Ruizhe Wang, Cheng Zhao, Zhenyu Ou, Lingxiao Chen","doi":"10.1038/s41397-025-00374-1","DOIUrl":"10.1038/s41397-025-00374-1","url":null,"abstract":"<p><p>Bladder cancer (BC) is a highly prevalent form of cancer worldwide, and cisplatin (CDDP) resistance poses a major challenge to patients. Cytoplasmic linker-associated protein 2 (CLASP2) is a member of the microtubule plus-end tracking protein family and is involved in the regulation of microtubule dynamics. In this study, we evaluated the influence of CLASP2 on BC progression and cisplatin resistance. Levels of CLASP2, HNRNPA1, NONO, ZRANB2, FUS, KHSRP and QKI in BC tissues and cells were tested by RT-qPCR. Protein levels of CLASP2 and KHSRP were detected by Western blot. Cell viability and IC50 of cisplatin-treated BC cells were measured by CCK-8. Cell proliferation and apoptosis were determined using colony formation assay and flow cytometry, respectively. RNA immunoprecipitation (RIP) and Co-immunoprecipitation (Co-IP) experiments were adopted to verify target genes of CLASP2. Cellular localization of CLASP2 and MAPRE1 was detected utilizing immunofluorescence staining. The xenograft tumor model was established in BALB/c nude mice. We found that iCLASP2 levels were increased in CDDP-resistant BC tissues and cells. Suppression of CLASP2 impeded BC cell proliferation and alleviated their resistance to CDDP. KHSRP positively influenced the stability of CLASP2 mRNA. There was a protein interaction between CLASP2 and MAPRE1. Silencing KHSRP or MAPRE1 reversed the effect exerted of CLASP2 on BC cells. CLASP2 decreased the sensitivity of BC to CDDP in vivo. Our results imply that CLASP2 contributes to tumorigenesis and cisplatin resistance in BC via targeting MAPRE1, thereby promoting BC progression and providing a new therapeutic target for BC treatment.</p>","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"25 3","pages":"14"},"PeriodicalIF":2.9,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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