Personalizing cancer therapy: the role of pharmacogenetics in overcoming drug resistance and toxicity.
Journal:
Molecular biology reports
Published Date:
Aug 2, 2025
Abstract
Cancer pharmacogenetics has become a cornerstone of precision oncology. It offers the potential to optimize therapeutic outcomes by tailoring treatments to individual genetic profiles. This review explores the central role of pharmacogenomics in addressing key challenges in cancer therapy, including drug resistance, variability in drug response between patients and chemotherapy-induced toxicity. We highlight key pharmacogenetic markers - such as DPYD, TPMT, UGT1A1, CYP2D6, ERCC1 and XRCC1 - that influence the metabolism, efficacy and toxicity of widely used chemotherapeutic agents. In addition, we discuss the role of ATP-binding cassette transporters (ABC transporters), including ABCB1, ABCG2 and ABCC2, in mediating drug resistance and their importance for personalized treatment strategies. Despite significant progress, the clinical translation of pharmacogenomics still faces several challenges. These include the need for large-scale validation of biomarkers in different populations, the integration of gene-environment interactions and the clarification of ethical and privacy concerns related to genetic testing. New technologies such as next-generation sequencing (NGS), liquid biopsies and artificial intelligence (AI)-based predictive models can overcome these obstacles by enabling real-time monitoring of tumor dynamics and refining personalized treatment protocols. The future of cancer pharmacogenetics lies in the integration of multi-omics data encompassing genomics, epigenomics, transcriptomics and proteomics to provide a comprehensive understanding of tumor biology and drug response. Collaboration between academic institutions, pharmaceutical companies and regulatory authorities is essential to establish standardized protocols for biomarker validation and expand pharmacogenomic databases. In addition, the development of ethical frameworks and patient-centered approaches will ensure the responsible integration of pharmacogenomics into clinical practice. By addressing current challenges and utilizing new technologies, cancer pharmacogenetics holds great promise for advancing precision oncology. This review highlights the importance of personalized medicine in improving therapeutic efficacy, minimizing adverse effects and ultimately improving patient outcomes in the fight against cancer.
