DPYD and UGT1A1 Pharmacogenetic Testing in Patients with Gastrointestinal Malignancies: An Overview of the Evidence and Considerations for Clinical Implementation.
DPYD and UGT1A1 Pharmacogenetic Testing in Patients with Gastrointestinal Malignancies: An Overview of the Evidence and Considerations for Clinical Implementation.
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DOI：
10.1002/phar.2463
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发表时间：
2020-11
期刊：
影响因子：
4.1
通讯作者：
Tuteja S
中科院分区：
文献类型：
--
作者：
Varughese LA;Lau-Min KS;Cambareri C;Damjanov N;Massa R;Reddy N;Oyer R;Teitelbaum U;Tuteja S
胃肠道（GI）恶性肿瘤是全球最常见的诊断癌症之一。尽管在治疗领域引入了靶向和免疫治疗药物，但细胞毒性药物，如氟嘧啶和伊立替康，仍然是许多这些肿瘤化疗的基石。药物遗传学（PGx）是一个快速发展的领域，占患者之间的药物代谢的差异，以预测治疗反应和毒性。考虑到与细胞毒性药物相关的严重治疗相关不良事件的显著发生率，使用PGx可以使临床医生更好地预测药物耐受性，同时最大限度地减少治疗中断或延迟。在这篇综述中，药物-基因对的PGx谱与潜在的影响，在胃肠道恶性肿瘤治疗- DPYD-5-氟尿嘧啶/卡培他滨和UGT 1A 1-伊立替康-和现有的临床证据，他们的作用，在减少严重不良事件进行了讨论。考虑临床实施，如最佳的实验室工作流程，电子健康记录集成，利益相关者的参与，以及供应商的教育，得到解决。最后，探索性PGx标志物在胃肠道恶性肿瘤治疗的描述。随着PGx知识库的迅速发展，药剂师将在利用其药理学知识和临床技能在临床中实施PGx测试方面发挥重要作用。
Gastrointestinal (GI) malignancies are among the most commonly diagnosed cancers worldwide. Despite the introduction of targeted and immunotherapy agents in the treatment landscape, cytotoxic agents, such as fluoropyrimidines and irinotecan, remain as the cornerstone of chemotherapy for many of these tumors. Pharmacogenetics (PGx) is a rapidly evolving field that accounts for interpatient variability in drug metabolism to predict therapeutic response and toxicity. Given the significant incidence of severe treatment-related adverse events associated with cytotoxic agents, utilizing PGx can allow clinicians to better anticipate drug tolerability while minimizing treatment interruptions or delays. In this review, the PGx profiles of drug-gene pairs with potential impact in GI malignancy therapy – DPYD-5-fluorouracil/capecitabine and UGT1A1-irinotecan – and the available clinical evidence of their roles in reducing severe adverse events are discussed. Considerations for clinical implementation, such as optimal laboratory workflows, electronic health record integration, and stakeholder engagement, as well as provider education, are addressed. Last, exploratory PGx markers in GI malignancy treatment are described. As the PGx knowledge base rapidly evolves, pharmacists will be vital in leveraging their pharmacology knowledge and clinical skills to implement PGx testing in the clinic.
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DOI：
10.1111/cts.12404
发表时间：
2016-10
期刊：
Clinical and translational science
影响因子：
--
作者：
Arwood MJ;Chumnumwat S;Cavallari LH;Nutescu EA;Duarte JD
通讯作者：
Duarte JD
DOI：
10.1038/tpj.2016.72
发表时间：
2017-01
期刊：
The pharmacogenomics journal
影响因子：
--
作者：
Bielinski SJ;St Sauver JL;Olson JE;Wieland ML;Vitek CR;Bell EJ;Mc Gree ME;Jacobson DJ;McCormick JB;Takahashi PY;Black JL;Caraballo PJ;Sharp RR;Beebe TJ;Weinshilboum RM;Wang L;Roger VL
通讯作者：
Roger VL
DOI：
10.2146/ajhp160030
发表时间：
2016-12-01
期刊：
American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
影响因子：
--
作者：
Hicks JK;Dunnenberger HM;Gumpper KF;Haidar CE;Hoffman JM
通讯作者：
Hoffman JM
影响因子：
6.2
作者：
Gold, Heather Taffet;Hall, Michael J.;Schackman, Bruce R.
通讯作者：
Schackman, Bruce R.
影响因子：
45.3
作者：
Cecchin, Erika;Innocenti, Federico;Toffoli, Giuseppe
通讯作者：
Toffoli, Giuseppe