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深入了解天冬酰胺酶过敏反应:探索药物遗传学影响。

Insights into Asparaginase Allergic Responses: Exploring Pharmacogenetic Influences.

作者信息

Cecconello Daiane Keller, Silva Klerize Anecely de Souza, de Senna Evelin Cristine Mendonça, Rechenmacher Ciliana, Daudt Liane Esteves, Michalowski Mariana Bohns

机构信息

Post Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil.

Translational Pediatrics Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil.

出版信息

Pharmaceutics. 2024 Aug 28;16(9):1134. doi: 10.3390/pharmaceutics16091134.

Abstract

Acute lymphoblastic leukemia represents the most prevalent childhood cancer. Modern chemotherapy has significantly improved outcomes, achieving EFS rates of 80% and OS rates nearing 90% in developed nations, while in developing regions, rates remain below 50%, highlighting disparities, and this difference is due to several factors. Genetic variability plays a role in these drug response disparities, presenting single-nucleotide variations (SNVs). Pharmacogenetic research aims to pinpoint these SNVs early in treatment to predict specific drug responses effectively. This review aims to explore advancements in pharmacogenetics associated with asparaginase (ASNase). ASNase plays a crucial role in the treatment of ALL and is available in three formulations: , , and PEG ASNase. ASNase therapy presents challenges due to adverse effects, like hypersensitivity reactions. Identifying predictive markers for hypersensitivity development beforehand is crucial for optimizing treatments. Several pharmacogenetic studies have investigated the association between SNVs and the risk of hypersensitivity. Key genes include , , , , , and . Studies have highlighted associations between SNVs within these genes and hypersensitivity reactions. Notably, most pharmacogenetic investigations of hypersensitivity have focused on patients treated with , emphasizing the need for broader exploration across different formulations. Future research investigating these variants holds promise for advancing our understanding of ASNase's pharmacogenetics.

摘要

急性淋巴细胞白血病是最常见的儿童癌症。现代化疗显著改善了治疗结果,在发达国家,无事件生存率(EFS)达到80%,总生存率(OS)接近90%,而在发展中地区,这一比率仍低于50%,凸显了差异,这种差异是由多种因素造成的。基因变异性在这些药物反应差异中起作用,表现为单核苷酸变异(SNV)。药物遗传学研究旨在在治疗早期确定这些SNV,以有效预测特定的药物反应。本综述旨在探讨与天冬酰胺酶(ASNase)相关的药物遗传学进展。ASNase在急性淋巴细胞白血病的治疗中起关键作用,有三种制剂: , ,以及聚乙二醇化天冬酰胺酶(PEG ASNase)。由于不良反应,如过敏反应,ASNase治疗存在挑战。预先确定过敏反应发生的预测标志物对于优化治疗至关重要。多项药物遗传学研究调查了SNV与过敏风险之间的关联。关键基因包括 , , , , ,以及 。研究强调了这些基因内的SNV与过敏反应之间的关联。值得注意的是,大多数关于过敏的药物遗传学研究都集中在接受 治疗的患者身上,强调需要对不同制剂进行更广泛的探索。未来对这些变异的研究有望增进我们对ASNase药物遗传学的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e416/11435241/29816bcc483b/pharmaceutics-16-01134-g001.jpg

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