SNPs in predicting clinical efficacy and toxicity of chemotherapy: walking through the quicksand.
SNPs in predicting clinical efficacy and toxicity of chemotherapy: walking through the quicksand.
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DOI：
10.18632/oncotarget.25256
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发表时间：
2018-05-18
期刊：
影响因子：
--
通讯作者：
Silvestris F
中科院分区：
文献类型：
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作者：
Palmirotta R;Carella C;Silvestris E;Cives M;Stucci SL;Tucci M;Lovero D;Silvestris F
在“精准医学”时代，化疗仍然是治疗许多癌症的支柱，但在临床实践中没有负担得起的预测化疗药物反应的指标。单核苷酸多态性（SNP）是发生在超过1%的完整人群中的基因序列变异，约占个体间基因组异质性的80%。许多研究已经调查了参与化疗药物的药效学和药代动力学的基因的SNP的预测作用，但是到目前为止，相关结果的临床实施是适度的。在检查的生殖系多态性变体中，二氢嘧啶脱氢酶（DPYD）和尿苷二磷酸葡萄糖醛酸转移酶（UGT）的几个SNP分别显示出作为基于氟嘧啶和/或伊立替康治疗后毒性预测因子的稳健作用，并且在治疗开始前强制检测一些指南。然而，在预测接受嘧啶类抗代谢物、铂类衍生物、伊立替康和紫杉烷类药物治疗的患者的疗效或毒性方面，其他基因（如MTHFR、TYMS、ERCC 1、XRCC 1、GSTP 1、CYP 3A 4/3A 5和ABCB 1）变体的能力报告了相反的结果。虽然目前还不能对这些SNPs进行常规检测，但当可用时，治疗决策确实可能受益于种系基因组信息。在这里，我们总结了生殖系基因组变异对主要化疗药物的疗效和毒性的临床影响，旨在促进临床医生在复杂的分子生物学概念和有争议的试验数据解释的odiern流沙领域的治疗预期。
In the “precision medicine” era, chemotherapy still remains the backbone for the treatment of many cancers, but no affordable predictors of response to the chemodrugs are available in clinical practice. Single nucleotide polymorphisms (SNPs) are gene sequence variations occurring in more than 1% of the full population, and account for approximately 80% of inter-individual genomic heterogeneity. A number of studies have investigated the predictive role of SNPs of genes enrolled in both pharmacodynamics and pharmacokinetics of chemotherapeutics, but the clinical implementation of related results has been modest so far. Among the examined germline polymorphic variants, several SNPs of dihydropyrimidine dehydrogenase (DPYD) and uridine diphosphate glucuronosyltransferases (UGT) have shown a robust role as predictors of toxicity following fluoropyrimidine- and/or irinotecan-based treatments respectively, and a few guidelines are mandatory in their detection before therapy initiation. Contrasting results, however, have been reported on the capability of variants of other genes as MTHFR, TYMS, ERCC1, XRCC1, GSTP1, CYP3A4/3A5 and ABCB1, in predicting either therapy efficacy or toxicity in patients undergoing treatment with pyrimidine antimetabolites, platinum derivatives, irinotecan and taxanes. While formal recommendations for routine testing of these SNPs cannot be drawn at this moment, therapeutic decisions may indeed benefit of germline genomic information, when available. Here, we summarize the clinical impact of germline genomic variants on the efficacy and toxicity of major chemodrugs, with the aim to facilitate the therapeutic expectance of clinicians in the odiern quicksand field of complex molecular biology concepts and controversial trial data interpretation.