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Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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开发DPYD基因定型方法,用于个性化胺治疗.

Betty Y L Wong1, Zhenyu Li2, Michael Jonathon Raphael3,4,5

  • 1Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

The journal of applied laboratory medicine
|December 12, 2023
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此摘要是机器生成的。

一种新的药物遗传学测试可以准确检测DPYD基因变异,识别高风险的患者,患有重度毒性. 这种分析有助于为癌症患者制定个性化治疗策略.

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科学领域:

  • 药物基因组学 药物基因组学
  • 分子诊断学 分子诊断
  • 在瘤学瘤学.

背景情况:

  • 罗皮里米丁药物是固体瘤的必要化疗剂.
  • 严重的毒性影响10-40%的患者接受胺治疗.
  • 破坏二皮里米丁脱酶活性的DPYD基因变异会增加毒性风险.

研究的目的:

  • 开发一种药物遗传测试,以选DPYD变体.
  • 识别患有皮里米丁诱导毒性的风险增加的患者.
  • 指导个性化胺治疗选择.

主要方法:

  • 开发了一种多重等位基因特异性聚合酶链反应 (AS-PCR) 试验.
  • 检测到五种常见的DPYD变异 (c.557A > G,c.1129-5923C > G,c.1679T > G,c.1905 + 1G > A,c.2846A > T). 在这些变异中,DPYD是最常见的.
  • 使用人口和熟练测试样本验证了测试,通过桑格测序证实.

主要成果:

  • 成功检测DPYD变体在未识别的人口和熟练程度样本中.
  • 测试表明,所有测试的变体都与桑格测序具有很高的一致性.
  • 确定了关键DPYD变异的异构体载体.

结论:

  • 建立了一个强大的多重AS-PCR试验,用于快速检测DPYD变种.
  • 该测试有效地选与胺毒性相关的DPYD变体.
  • 这种测试通过识别有风险的患者以获得更安全的化疗来支持个性化医疗.