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癌症治疗中的种系变异

Germline variants in cancer therapy.

作者信息

Kaehler Meike, Cascorbi Ingolf

机构信息

Institute for Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel D-24105, Germany.

出版信息

Cancer Drug Resist. 2019 Mar 19;2(1):18-30. doi: 10.20517/cdr.2019.05. eCollection 2019.

Abstract

Cancer pharmacogenetics implies a complex combination of germline variants from the patient and somatic mutations in tumor cells. Somatic mutations meanwhile have become drugable targets or biomarkers, whereas germline mutations potentially predict adverse drug effects or drug response. Here, we evaluate hereditary variants in biotransforming enzymes and drug transporters, such as thiopurine S-methyltransferase, UDP-glucuronosyltransferase (), dihydropyrimidine dehydrogenase (), as well as ABC transporters (, and subfamily) with respect to cytostatics and targeted therapies. Furthermore, gene expression regulation with regards to epigenetics and posttranscriptional modification are discussed.

摘要

癌症药物遗传学意味着患者种系变异与肿瘤细胞体细胞突变的复杂组合。同时,体细胞突变已成为可用药靶点或生物标志物,而种系突变可能预测药物不良反应或药物反应。在此,我们评估生物转化酶和药物转运体中的遗传变异,如硫嘌呤甲基转移酶、尿苷二磷酸葡萄糖醛酸基转移酶、二氢嘧啶脱氢酶,以及ABC转运体(A、B和C亚家族)在细胞毒性药物和靶向治疗方面的情况。此外,还讨论了表观遗传学和转录后修饰方面的基因表达调控。

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Germline variants in cancer therapy.癌症治疗中的种系变异
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