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Is Monitoring of the Intracellular Active Metabolite Levels of Nucleobase and Nucleoside Analogs Ready for Precision Medicine Applications?

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Abstract

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.

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  1. Shenjia Huang and Yicong Bian contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Pharmacology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China

    Yicong Bian, Chenrong Huang & Liyan Miao

  2. Department of Clinical Pharmacy, College of Pharmaceutical Science, Soochow University, Suzhou, China

    Shenjia Huang, Yicong Bian, Chenrong Huang & Liyan Miao

  3. Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University, Suzhou, China

    Shenjia Huang, Yicong Bian, Chenrong Huang & Liyan Miao

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This work was supported by the National Natural Science Foundation of China (81773820), the National Key New Drug Creation Special Programs (2017ZX09304-021), Suzhou Talent Research Project (GSWS2019036), and Hospital Pharmacy Committee of Chinese Pharmaceutical Association (CPA-Z05-ZC-2021-002).

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Chenrong Huang and Shenjia Huang had the idea for the article. Shenjia Huang and Yicong Bian performed the literature search, and drafted and wrote the manuscript. Chenrong Huang and Liyan Miao critically revised the manuscript.

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Huang, S., Bian, Y., Huang, C. et al. Is Monitoring of the Intracellular Active Metabolite Levels of Nucleobase and Nucleoside Analogs Ready for Precision Medicine Applications?. Eur J Drug Metab Pharmacokinet 47, 761–775 (2022). https://doi.org/10.1007/s13318-022-00786-5

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