Pharmacogenomics insights into precision pediatric oncology

Kristie N. Ramos, David Gregornik, Kenneth S. Ramos

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

PURPOSE OF REVIEW: Pharmacogenomic insights provide an opportunity to optimize medication dosing regimens and patient outcomes. However, the potential for interindividual genomic variability to guide medication dosing and toxicity monitoring is not yet standard of care. In this review, we present advances for the thiopurines, anthracyclines and vincristine and provide perspectives on the actionability of pharmacogenomic guidance in the future. RECENT FINDINGS: The current guideline on thiopurines recommends that those with normal predicted thiopurine methyltransferase and NUDT15 expression receive standard-of-care dosing, while 'poor metabolizer' haplotypes receive a decreased 6-mercaptopurine starting dose to avoid bone marrow toxicity. Emerging evidence established significant polygenic contributions that predispose to anthracycline-induced cardiotoxicity and suggest this knowledge be used to identify those at higher risk of complications. In the case of vincristine, children who express CYP3A5 have a significantly reduced risk of peripheral neuropathy compared with those expressing an inactive form or the CYP3A4 isoform. SUMMARY: The need for adequately powered pediatric clinical trials, coupled with the study of epigenetic mechanisms and their influence on phenotypic variation and the integration of precision survivorship into precision approaches are featured as important areas for focused investments in the future.

Original languageEnglish (US)
Pages (from-to)564-569
Number of pages6
JournalCurrent opinion in pediatrics
Volume33
Issue number6
DOIs
StatePublished - Dec 1 2021

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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