Scholarlink

<p>Imatinib is associated with significant toxicities, including myelosuppression, oedema, and hypersensitivity, with considerable interpatient variability. Pharmacokinetic and pharmacogenomic factors contribute, but comprehensive biomarkers are yet to be identified. A retrospective cohort study was conducted on 154 gastrointestinal stromal tumour (GIST) patients receiving imatinib. Steady-state concentrations of imatinib and its metabolite were measured using liquid chromatography-tandem mass spectrometry. Thirty-five genetic polymorphisms in signaling, transporter, and immune genes were genotyped, and multivariate logistic regression was performed, adjusting for clinical covariates. The study found a significant correlation between myelosuppression and imatinib plasma concentration, along with genetic polymorphisms in <i>FLT1</i>, <i>MAPK1</i>, <i>PDGFRB</i>, and <i>SHC1</i>. Peripheral oedema was more prevalent in females and associated with <i>PDGFRB</i> polymorphisms. Hypersensitivity was linked to <i>EGFR</i> and <i>CXCL14</i> polymorphisms. These findings identify novel pharmacogenetic markers for imatinib-induced toxicities, supporting the potential of personalized treatment strategies through genetic testing and therapeutic drug monitoring. Further validation in larger cohorts is needed.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genetic and pharmacokinetic factors associated with imatinib-induced toxicities in gastrointestinal stromal tumors

  • 期刊论文

  • 发表日期：

    2025年11月5日

查看全文
  • Wei Zhuang,
  • Yi Zeng,
  • Xinping Lin,
  • Haibo Qiu,
  • Wanlong Lin,
  • Min Huang,
  • Xueding Wang

摘要

Imatinib is associated with significant toxicities, including myelosuppression, oedema, and hypersensitivity, with considerable interpatient variability. Pharmacokinetic and pharmacogenomic factors contribute, but comprehensive biomarkers are yet to be identified. A retrospective cohort study was conducted on 154 gastrointestinal stromal tumour (GIST) patients receiving imatinib. Steady-state concentrations of imatinib and its metabolite were measured using liquid chromatography-tandem mass spectrometry. Thirty-five genetic polymorphisms in signaling, transporter, and immune genes were genotyped, and multivariate logistic regression was performed, adjusting for clinical covariates. The study found a significant correlation between myelosuppression and imatinib plasma concentration, along with genetic polymorphisms in FLT1, MAPK1, PDGFRB, and SHC1. Peripheral oedema was more prevalent in females and associated with PDGFRB polymorphisms. Hypersensitivity was linked to EGFR and CXCL14 polymorphisms. These findings identify novel pharmacogenetic markers for imatinib-induced toxicities, supporting the potential of personalized treatment strategies through genetic testing and therapeutic drug monitoring. Further validation in larger cohorts is needed.