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Updated: May 14, 2025

Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay EMSA and DNA-affinity Precipitation Assay DAPA
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Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay EMSA and DNA-affinity Precipitation Assay DAPA

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Genetic variants in NUDT15 gene their clinical implications in cancer therapy

Yazun Jarrar1, Maria Ghishan2, Fatima Khirfan2

  • 1Department of Basic Medical Sciences, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.

Drug Metabolism and Personalized Therapy
|April 12, 2025
PubMed

Insights

Genetic variations in Nudix Hydrolase 15 (NUDT15) impact thiopurine drug metabolism and toxicity. Understanding these NUDT15 variants is crucial for personalized cancer therapy and improved patient outcomes.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Thiopurine anticancer drugs exhibit variable patient responses due to genetic and environmental factors.
  • Genetic variations in Nudix Hydrolase 15 (NUDT15) significantly influence thiopurine metabolism, affecting drug efficacy and toxicity.
  • Despite known impacts, a comprehensive analysis of NUDT15 variants in thiopurine therapy is lacking.

Purpose of the Study:

  • To conduct a thorough analysis of NUDT15 genetic variants and their clinical significance in thiopurine therapy.
  • To synthesize findings from existing clinical studies and predict functional effects of uncertain variants using in silico methods.
  • To provide a foundation for integrating NUDT15 genetic information into clinical practice for personalized cancer treatment.

Main Methods:

  • Literature review of clinical studies on NUDT15 variants and thiopurine therapy.
  • In silico analysis to predict the functional impact of NUDT15 variants with uncertain significance.
  • Synthesis of data to evaluate the role of NUDT15 in thiopurine metabolism and patient outcomes.

Main Results:

  • NUDT15 genetic variations are key determinants of thiopurine drug response, influencing efficacy and toxicity.
  • Specific NUDT15 variants are associated with increased risk of adverse events like myelosuppression.
  • In silico predictions aid in understanding the functional consequences of previously uncharacterized NUDT15 variants.

Conclusions:

  • Comprehensive analysis of NUDT15 variants is essential for optimizing thiopurine therapy.
  • Integrating NUDT15 genetic testing into clinical practice can reduce toxicity and improve therapeutic outcomes.
  • Further research into NUDT15 interactions with metabolic pathways will advance personalized medicine in oncology.
Keywords:
NUDT15anticancer drugsdrug metabolismpersonalized therapythiopurine derivatives

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