Genetic variants in NUDT15 gene their clinical implications in cancer therapy.

Abstract

Individual variations in the response to thiopurine-based anticancer drugs are influenced by genetic and environmental factors, making it challenging to optimize dosing and minimize toxicity. Among the key genes involved, genetic variations in the nudix hydrolase 15 (NUDT15) gene affect on thiopurine metabolism, thus influencing drug efficacy and the risk of severe adverse effects, such as myelosuppression, These variations also contribute to inter-individual differences in drug tolerance and clinical outcomes. Despite the recognized impact of NUDT15 variations, there has been limited comprehensive exploration of these variants and their clinical significance in thiopurine therapy. This review provides a thorough analysis of NUDT15 genetic variants by synthesizing findings from prior clinical studies and employing in silico analyses to predict the functional effects of variants with uncertain significance. Comprehensive analysis of NUDT15 variants and their interactions with other metabolic pathways could offer valuable insights for advancing personalized medicine in cancer treatment. This review aims to establish a foundation for integrating NUDT15 genetic information into the clinical practice, reducing toxicity, and improved therapeutic outcomes in patients undergoing thiopurine-based chemotherapy.