超越DPYD的基因组指导剂量:多基因算法的时间?
Anthi Maslarinou1,2, Vangelis G Manolopoulos1,2,3, Georgia Ragia1,2
1Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
Frontiers in pharmacology
|May 31, 2023
概括
甲胺 (FP) 化疗可以引起严重的毒性. 除了DPYD之外的遗传因素影响FP毒性风险,建议扩大药物基因组指导方针,以确保更安全的处方.
科学领域:
- 药物基因组学 药物基因组学
- 在瘤学瘤学.
- 药物新陈代谢 药物新陈代谢
背景情况:
- 类皮里米丁 (FPs),包括5-甲 (5-FU) 和capecitabine (CAP),是固体瘤的重要化疗剂.
- 患者的反应和毒性受到遗传变异的显著影响,特别是在二胺酸脱酶 (DPYD) 基因中.
- 目前基于DPYD的指导方针建议对酶活性有缺陷的患者进行剂量调整.
研究的目的:
- 审查目前关于FP相关基因的药理基因组学知识,超出DPYD.
- 专注于影响FP毒性风险和剂量减少策略的遗传因素.
- 提出改善FP药物治疗的未来方向.
主要方法:
- 与胺相关的药物基因组学研究的文献综述.
- 对影响FP药理动力学和药理动力学的遗传变异的分析.
- 评估现有的基于DPYD的剂量指南.
主要成果:
- 除DPYD以外的基因的遗传变异有助于FP诱导的毒性.
- 这些额外的遗传因素影响FP的药理动力学和药理动力学.
- 将更多的基因变异纳入剂量指南可能会提高FP的安全性和有效性.
结论:
- 药物遗传学指南应该扩展到DPYD之外,包括其他相关基因.
- 未来的指导方针可能会从纳入基于种族的遗传面板和基因*基因/性别*基因相互作用中受益.
- 个性化FP剂量策略对于最小化毒性和优化治疗结果至关重要.
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