Department of Clinical Pharmacy, College of Pharmaceutical Science, Soochow University, Suzhou, China.
Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University, Suzhou, China.
Eur J Drug Metab Pharmacokinet. 2022 Nov;47(6):761-775. doi: 10.1007/s13318-022-00786-5. Epub 2022 Aug 1.
Nucleobase and nucleoside analogs (NAs) play important roles in cancer therapy. Although there are obvious individual differences in NA treatments, most NAs lack direct relationships between their plasma concentration and efficacy or adverse effects. Accumulating evidence suggests that the intracellular active metabolite levels of NAs predict patient outcomes. This article reviewed the relationships between NA intracellular active metabolite levels and their efficacy or adverse effects. The factors affecting the formation of intracellular active metabolites and combination regimens that elevate intracellular active metabolite levels were also reviewed. Given the mechanism of NA cytotoxicity, NA intracellular active metabolite levels may be predictive of clinical outcomes. Many clinical studies support this hypothesis. Therefore, the monitoring of intracellular active metabolite levels is beneficial for individualized NA treatment. However, to perform clinical monitoring in practice, well-designed studies are needed to explore the optimal threshold or range and the appropriate regimen adjustment strategies based on these parameters.
核苷类似物（NAs）在癌症治疗中起着重要作用。尽管 NA 治疗存在明显的个体差异，但大多数 NAs 缺乏其血浆浓度与疗效或不良反应之间的直接关系。越来越多的证据表明，NAs 的细胞内活性代谢物水平可预测患者的预后。本文综述了 NA 细胞内活性代谢物水平与其疗效或不良反应之间的关系。还综述了影响细胞内活性代谢物形成的因素以及提高细胞内活性代谢物水平的联合方案。鉴于 NA 细胞毒性的机制，NA 细胞内活性代谢物水平可能是临床结局的预测因素。许多临床研究支持这一假设。因此，监测细胞内活性代谢物水平有助于实现 NA 的个体化治疗。然而，为了在实践中进行临床监测，需要进行精心设计的研究，以探索基于这些参数的最佳阈值或范围以及适当的方案调整策略。
