Testing for Dihydropyrimidine Dehydrogenase Deficiency to Individualize 5-Fluorouracil Therapy.
Testing for Dihydropyrimidine Dehydrogenase Deficiency to Individualize 5-Fluorouracil Therapy.
复制标题
检测二氢嘧啶脱氢酶缺乏症以确定5-氟尿嘧啶的个体化治疗。
作者：
5-氟尿嘧啶(5-FU)是一种常用于治疗多种癌症的化疗药物。许多接受5-FU治疗的人都会经历这种药物的严重毒性，在严重的情况下，患者可能会死亡。这篇综述讨论了目前识别5-FU治疗严重副作用的高危人群的方法。与使用常用化疗药物5-氟尿嘧啶(5-FU)有关的严重不良事件(毒性)影响三分之一的患者，是过早停止治疗的主要原因。在过去的30年里，5-FU分解代谢酶二氢嘧啶脱氢酶(DPD，由DPYD编码)的缺乏被认为是一种与5-FU毒性高风险相关的药物遗传综合征。接受以5-FU为基础的化疗的DPD缺乏症患者中有相当一部分死于毒性。在这篇手稿中，我们回顾了识别DPD缺乏症的可操作标记物的最新进展，以及将这些标记物整合到临床决策过程中的现状。目前可用的测试的局限性，以及治疗前DPYD测试的监管状况，也进行了讨论。
5-Fluorouracil (5-FU) is a chemotherapy drug that is commonly used to treat multiple cancers. Many people who are treated with 5-FU experience severe toxicity to the drug, and in severe cases, patients can die. This review discusses current methods for identifying people who are at high risk for severe side effects to 5-FU therapy. Severe adverse events (toxicity) related to the use of the commonly used chemotherapeutic drug 5-fluorouracil (5-FU) affect one in three patients and are the primary reason cited for premature discontinuation of therapy. Deficiency of the 5-FU catabolic enzyme dihydropyrimidine dehydrogenase (DPD, encoded by DPYD) has been recognized for the past 3 decades as a pharmacogenetic syndrome associated with high risk of 5-FU toxicity. An appreciable fraction of patients with DPD deficiency that receive 5-FU-based chemotherapy die as a result of toxicity. In this manuscript, we review recent progress in identifying actionable markers of DPD deficiency and the current status of integrating those markers into the clinical decision-making process. The limitations of currently available tests, as well as the regulatory status of pre-therapeutic DPYD testing, are also discussed.