Pharmacogenomic biomarkers in oncology: evidence, clinical utility, and barriers to implementation.

Germline variants in DPYD, TPMT, NUDT15 and UGT1A1 determining chemotherapy metabolism, transport and toxicity, distinguished from somatic alterations in EGFR, RAS, BRAF and HER2 that drive treatment selection.

This review offers a critical evaluation of clinically validated pharmacogenomic biomarkers in oncology, combining somatic alterations that determine tumour sensitivity with germline variants governing drug metabolism, transport and toxicity. The authors highlight DPYD, TPMT, NUDT15 and UGT1A1 as the key germline determinants of genotype-guided dosing, presented as a means of improving safety without compromising efficacy. Somatic biomarkers EGFR, RAS, BRAF and HER2 remain central to treatment selection, with emerging resistance justifying iterative molecular reassessment. The review proposes a tiered implementation framework and discusses barriers to progress along with future directions, including polygenic models, multi-omics approaches and artificial intelligence.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The main weakness of this synthesis is to bring under one label two objects that share neither evidence level nor clinical pathway: germline pharmacogenetics of toxicity, where DPYD and UGT1A1 call for testing before prescription, and somatic biomarkers of tumour selection, which belong to routine oncology. No literature search strategy is described and the tiered implementation framework is not validated: this is orienting reading, not a source of evidence. It serves newcomers to the field well; for anyone deciding on a test it adds nothing that dedicated guidelines do not state better.

Analysis by Dr Thibaut Benquey