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在一个多样化的澳大利亚儿科肿瘤队列中鉴定出的高风险药物基因组学表型的频率及影响

Frequency and Implications of High-Risk Pharmacogenomic Phenotypes Identified in a Diverse Australian Pediatric Oncology Cohort.

作者信息

Moore Claire, Halman Andreas, Stenta Tayla, Khatri Dhrita, Williams Elizabeth, Dyas Roxanne, Stolper Julian, Elliott David A, Conyers Rachel

机构信息

Cancer Therapies, Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.

出版信息

Clin Transl Sci. 2025 May;18(5):e70246. doi: 10.1111/cts.70246.

Abstract

Pharmacogenomics remains underutilized in pediatric oncology, despite the existence of evidence-based guidelines. Implementation of pharmacogenomics-informed prescribing could improve medication safety and efficacy in pediatric oncology patients, who are at high risk of adverse drug reactions. This study examines the prevalence of high-risk pharmacogenomic phenotypes and the prescription of relevant medications in a diverse Australian pediatric oncology cohort, highlighting the potential impact of pharmacogenomic testing in this unique population. Whole genome sequencing data from 180 patients were analyzed to assess 14 genes with evidence-based pharmacogenomic guidelines relevant to pediatric oncology. Over 90% of patients had at least one high-risk phenotype, with 20% presenting four or more. Ondansetron, mercaptopurine, omeprazole, pantoprazole, and voriconazole were commonly prescribed medications that have pharmacogenomic prescribing recommendations, with the latter three showing the highest actionability rates. High-risk phenotypes were most frequently observed for CYP2C19 and CYP2D6, with 30% of patients having a high-risk phenotype for both genes. This study underscores the potential utility of pharmacogenomics in pediatric oncology patients across a range of pharmacogenes and commonly prescribed medications. The findings support advocacy for implementing broad, pre-emptive pharmacogenomic testing in oncology patients to improve treatment safety and efficacy.

摘要

尽管有循证指南,但药物基因组学在儿科肿瘤学中的应用仍然不足。实施基于药物基因组学的处方可以提高儿科肿瘤患者的用药安全性和有效性,这些患者发生药物不良反应的风险很高。本研究调查了澳大利亚一个多样化的儿科肿瘤队列中高风险药物基因组学表型的患病率以及相关药物的处方情况,突出了药物基因组检测在这一独特人群中的潜在影响。分析了180名患者的全基因组测序数据,以评估14个与儿科肿瘤学相关的有循证药物基因组学指南的基因。超过90%的患者至少有一种高风险表型,20%的患者有四种或更多高风险表型。昂丹司琼、巯嘌呤、奥美拉唑、泮托拉唑和伏立康唑是有药物基因组学处方建议的常用药物,后三种药物的可操作性率最高。CYP2C19和CYP2D6的高风险表型最为常见,30%的患者这两个基因都有高风险表型。本研究强调了药物基因组学在一系列药物基因和常用药物的儿科肿瘤患者中的潜在效用。这些发现支持在肿瘤患者中实施广泛的、先发制人的药物基因组检测以提高治疗安全性和有效性的主张。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70b4/12065477/3c1a92025f46/CTS-18-e70246-g001.jpg

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