Pharmacogenetics in pediatric oncology: Current evidence and challenges for clinical implementation

To review the pharmacogenetic evidence associated with the main antineoplastic agents used in pediatric oncology, identify the biomarkers with the greatest clinical applicability, and examine the key factors influencing their implementation in routine clinical practice.

A bibliographic review was conducted on pharmacogenetics in pediatric oncology. The following sources were searched: PubMed/MEDLINE, the ClinPGx database, and the major international clinical guidelines, including those of the Clinical Pharmacogenetics Implementation Consortium, the Dutch Pharmacogenetics Working Group, and the Canadian Pharmacogenomics Network for Drug Safety. Recommendations from the Spanish Society of Pharmacogenetics and Pharmacogenomics and the Common Catalog of Genetic and Genomic Tests of the Spanish National Health System were additionally reviewed.

Six gene-drug pairs or drug groups of particular relevance to pediatric oncology were identified. The TPMT/NUDT15-thiopurine, DPYD-fluoropyrimidine, and UGT1A1-irinotecan associations carry the highest level of evidence. These are supported by international clinical guidelines and are included in the Spanish Catalog of Genetic and Genomic Tests. Pediatric-specific evidence for irinotecan, however, remains limited, constraining the direct extrapolation of existing recommendations to this population. Biomarkers related to anthracyclines, methotrexate, and cisplatin show more heterogeneous evidence and a lower degree of clinical validation. Notably, anthracyclines and cisplatin have specific Canadian Pharmacogenomics Network for Drug Safety recommendations, and for methotrexate, variants such as those in SLCO1B1 may help identify patients at increased risk of toxicity. The review further highlights that the clinical utility of pharmacogenetics in pediatrics is shaped by developmental factors such as ontogeny, as well as by phenoconversion, both of which can alter genotype-phenotype concordance and limit the applicability of evidence derived from adult studies.

Pharmacogenetics represents a promising tool for optimizing the efficacy and safety of antineoplastic treatment in children. However, its implementation in clinical practice will require generating pediatric-specific evidence and incorporating genetic data alongside dynamic factors such as ontogeny and phenoconversion into multidisciplinary precision medicine frameworks, within which the hospital pharmacist has a meaningful role to play.