Genetic variations that influence paclitaxel pharmacokinetics and intracellular effects that may contribute to chemotherapy-induced neuropathy: A narrative review.
Genetic variations that influence paclitaxel pharmacokinetics and intracellular effects that may contribute to chemotherapy-induced neuropathy: A narrative review.
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DOI：
10.3389/fpain.2023.1139883
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发表时间：
2023
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影响因子：
--
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--
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紫杉烷类，特别是紫杉醇和多西紫杉醇，是常用于治疗乳腺癌的化疗剂。化疗引起的周围神经病变 (CIPN) 是一种常见的副作用，在所有接受治疗的患者中，高达 70% 的患者会出现这种情况，并影响治疗期间和治疗后的生活质量。 CIPN 表现为手套和袜子感觉缺陷以及运动和自主功能减弱。轴突较长的神经发生 CIPN 的风险较高。 CIPN 的病因是多因素的，且人们对其知之甚少，这限制了治疗选择。病理生理机制可包括：（i）线粒体和细胞内微管功能的破坏，（ii）轴突形态的破坏，以及（iii）小胶质细胞和其他免疫细胞反应的激活等。最近的工作探讨了遗传变异的贡献以及对紫杉烷类药物的反应所选择的表观遗传变化，以深入了解它们与 CIPN20 病理生理机制的关系，希望能够识别出预测性和可靶向的生物标志物。尽管前景广阔，但许多 CIPN 遗传学研究不一致，因此难以开发可靠的 CIPN 生物标志物。本叙述性综述的目的是对现有证据进行基准测试，并确定遗传变异在影响紫杉醇药代动力学和可能与 CIPN 发展相关的细胞膜转运中的作用的理解差距。
Taxanes, particularly paclitaxel and docetaxel, are chemotherapeutic agents commonly used to treat breast cancers. A frequent side effect is chemotherapy-induced peripheral neuropathy (CIPN) that occurs in up to 70% of all treated patients and impacts the quality of life during and after treatment. CIPN presents as glove and stocking sensory deficits and diminished motor and autonomic function. Nerves with longer axons are at higher risk of developing CIPN. The causes of CIPN are multifactorial and poorly understood, limiting treatment options. Pathophysiologic mechanisms can include: (i) disruptions of mitochondrial and intracellular microtubule functions, (ii) disruption of axon morphology, and (iii) activation of microglial and other immune cell responses, among others. Recent work has explored the contribution of genetic variation and selected epigenetic changes in response to taxanes for any insights into their relation to pathophysiologic mechanisms of CIPN20, with the hope of identifying predictive and targetable biomarkers. Although promising, many genetic studies of CIPN are inconsistent making it difficult to develop reliable biomarkers of CIPN. The aims of this narrative review are to benchmark available evidence and identify gaps in the understanding of the role genetic variation has in influencing paclitaxel's pharmacokinetics and cellular membrane transport potentially related to the development of CIPN.
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影响因子：
5.6
作者：
Di Francia R;Atripaldi L;Di Martino S;Fierro C;Muto T;Crispo A;Rossetti S;Facchini G;Berretta M
通讯作者：
Berretta M
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：
5.8
作者：
Kugler, Nicole;Klein, Kathrin;Zanger, Ulrich M.
通讯作者：
Zanger, Ulrich M.
影响因子：
2.8
作者：
Leskelae, S.;Jara, C.;Rodriguez-Antona, C.
通讯作者：
Rodriguez-Antona, C.
DOI：
10.1158/1078-0432.ccr-18-0656
发表时间：
2018-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hertz DL;Kidwell KM;Vangipuram K;Li F;Pai MP;Burness M;Griggs JJ;Schott AF;Van Poznak C;Hayes DF;Lavoie Smith EM;Henry NL
通讯作者：
Henry NL