Exploring pharmacogenetics of paclitaxel- and docetaxel-induced peripheral neuropathy by evaluating the direct pharmacogenetic-pharmacokinetic and pharmacokinetic-neuropathy relationships.
Exploring pharmacogenetics of paclitaxel- and docetaxel-induced peripheral neuropathy by evaluating the direct pharmacogenetic-pharmacokinetic and pharmacokinetic-neuropathy relationships.
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通过评估药物遗传学-药代动力学和药代动力学-神经病变的直接关系，探讨紫杉醇和多西他赛诱导的周围神经病变的药物遗传学。
DOI：
10.1080/17425255.2021.1856367
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发表时间：
2021-03
影响因子：
4.3
通讯作者：
Hertz DL
中科院分区：
文献类型：
--
作者：
Hertz DL
周围神经病(PN)是包括紫杉烷在内的几种化疗药物的衰弱不良反应。预测PN的生物标志物可以指导个体化紫杉烷治疗，以减少PN，提高治疗结果。紫杉烷诱导的PN的药物遗传学研究主要集中在参与紫杉烷药代动力学的基因，包括酶和转运蛋白。这些研究的高度矛盾的发现阻碍了遗传生物标记物的临床实践。本文通过评估两个独立的、直接关联的证据，即药物遗传学对紫杉烷药代动力学的影响，以及紫杉烷药代动力学影响PN的证据，讨论了识别PN的药物遗传学预测因素的进展。评估这些直接关系使读者能够了解个性化紫杉烷治疗的进展和未来研究的机会。紫杉醇的药代动力学是PN的主要决定因素。还需要更多的临床试验来确认个体化给药的临床益处，以实现紫杉醇的目标暴露。遗传因素对紫杉醇的药代动力学没有重要影响，也可能无助于指导给药。然而，遗传学可能有助于PN敏感性，并可能有助于估计患者的最佳紫杉醇暴露。对于多西紫杉醇，遗传学尚未被证明对药代动力学有意义的影响，也没有证据表明药代动力学决定PN。
Peripheral neuropathy (PN) is a debilitating adverse effect of several classes of chemotherapy including the taxanes. Predictive biomarkers of PN could inform individualized taxane treatment to reduce PN and enhance therapeutic outcomes. Pharmacogenetics studies of taxane-induced PN have focused on genes involved in taxane pharmacokinetics, including enzymes and transporters. Highly contradictory findings from these studies prevents translation of genetic biomarkers into clinical practice. This review discusses the progress toward identifying pharmacogenetic predictors of PN by assessing the evidence for two independent, direct associations; the effect of pharmacogenetics on taxane pharmacokinetics and the evidence that taxane pharmacokinetics affects PN. Assessing these direct relationships allows the reader to understand the progress toward individualized taxane treatment and opportunities for future research. Paclitaxel pharmacokinetics is a major determinant of PN. Additional clinical trials are needed to confirm the clinical benefit of individualized dosing to achieve target paclitaxel exposure. Genetics does not meaningfully contribute to paclitaxel pharmacokinetics and may not be useful to inform dosing. However, genetics may contribute to PN sensitivity and could be useful for estimating patients’ optimal paclitaxel exposure. For docetaxel, genetics has not been demonstrated to have a meaningful effect on pharmacokinetics and there is no evidence that pharmacokinetics determines PN.
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DOI：
10.1158/1078-0432.ccr-12-3786
发表时间：
2013-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
de Graan AJ;Elens L;Sprowl JA;Sparreboom A;Friberg LE;van der Holt B;de Raaf PJ;de Bruijn P;Engels FK;Eskens FA;Wiemer EA;Verweij J;Mathijssen RH;van Schaik RH
通讯作者：
van Schaik RH
影响因子：
6.7
作者：
Chua KC;Xiong C;Ho C;Mushiroda T;Jiang C;Mulkey F;Lai D;Schneider BP;Rashkin SR;Witte JS;Friedman PN;Ratain MJ;McLeod HL;Rugo HS;Shulman LN;Kubo M;Owzar K;Kroetz DL
通讯作者：
Kroetz DL
影响因子：
11.2
作者：
Beutler, Andreas S.;Kulkarni, Amit A.;Kanwar, Rahul;Klein, Christopher J.;Therneau, Terry M.;Qin, Rui;Banck, Michaela S.;Boora, Ganesh K.;Ruddy, Kathryn J.;Wu, Yanhong;Smalley, Regenia L.;Cunningham, Julie M.;Le-Lindqwister, Nguyet Anh;Beyerlein, Peter;Schroth, Gary P.;Windebank, Anthony J.;Zuechner, Stephan;Loprinzi, Charles L.
通讯作者：
Loprinzi, Charles L.
影响因子：
45.3
作者：
Bruno, R;Hille, D;Sheiner, LB
通讯作者：
Sheiner, LB
DOI：
10.1097/00008571-200110000-00006
发表时间：
2001-10-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Dai, D;Zeldin, DC;Goldstein, JA
通讯作者：
Goldstein, JA