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

TPMT, NUDT15, DPYD, UGT1A1

Gene-drug pairs of pediatric antineoplastic agents: TPMT/NUDT15 and thiopurines, DPYD and fluoropyrimidines, UGT1A1 and irinotecan

This literature review summarizes the pharmacogenetic evidence for the main antineoplastic agents used in pediatric oncology and the factors shaping its implementation in routine practice. Sources were PubMed/MEDLINE, the ClinPGx database and major international guidelines (CPIC, DPWG, Canadian Pharmacogenomics Network for Drug Safety), supplemented by recommendations from the Spanish Society of Pharmacogenetics and Pharmacogenomics and the Common Catalog of Genetic and Genomic Tests of the Spanish National Health System. Six gene-drug pairs or drug groups were identified; TPMT/NUDT15 and thiopurines, DPYD and fluoropyrimidines, and UGT1A1 and irinotecan carry the highest level of evidence, although pediatric-specific evidence for irinotecan remains limited. Biomarkers for anthracyclines, methotrexate and cisplatin rest on more heterogeneous evidence, although anthracyclines and cisplatin have specific Canadian recommendations and SLCO1B1 variants may identify patients at increased risk of methotrexate toxicity. The authors stress that ontogeny and phenoconversion alter genotype-phenotype concordance in children and limit the applicability of adult-derived evidence.

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

A narrative review without explicit selection criteria, but with a clear and directly usable hierarchy: three gene-drug pairs are ready for pediatric practice, the others still belong to research. The most useful part concerns ontogeny: the functional translation of a genotype varies with age, and pediatric data are precisely what is missing for irinotecan.

Analysis by Dr Thibaut Benquey