Pharmacogenomic biomarkers in oncology: evidence, clinical utility, and barriers to implementation.
TL;DR
A critical evaluation of clinically validated PGx biomarkers for chemotherapeutics and targeted therapy with a focus on translational relevance and strength of evidence shows high-impact germline markers such as DPYD, TPMT, NUDT15 and UGT1A1 are highlighted as key determinants of genotype-guided dosing for improving safety without compromising efficacy.
Abstract
Interpatient variability in chemotherapy response and toxicity remains a major challenge in oncology. Pharmacogenomics (PGx) is an approach to address this challenge by combining somatic alterations that affect tumour sensitivity with germline variants that affect drug metabolism, transport and toxicity. This review provides a critical evaluation of clinically validated PGx biomarkers for chemotherapeutics and targeted therapy with a focus on translational relevance and strength of evidence. High-impact germline markers such as DPYD, TPMT, NUDT15 and UGT1A1 are highlighted as key determinants of genotype-guided dosing for improving safety without compromising efficacy. Somatic biomarkers such as EGFR, RAS, BRAF, and HER2 remain central to treatment selection, while resistance underscores the need for ongoing molecular assessment. A tiered implementation framework, barriers to progress, and future directions involving polygenic models, multi-omics, and artificial intelligence (AI) are discussed to advance safe, effective, and personalized chemotherapy.