Related Experiment Video
Updated: Jun 11, 2026
09:33
Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
Published on: August 25, 2023
Practical guide to implementing pre-emptive pharmacogenetic screening in routine pediatric oncology care
Emma C Bernsen1, Lidwien M Hanff1, Theodorus W Kouwenberg1
1Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.
Pharmacogenomics
|June 9, 2026
Summary
Pre-emptive pharmacogenetics (PGx) screening in pediatric oncology helps tailor drug doses, improving treatment. Implementation in the Netherlands involved adapting infrastructure and integrating genetic data into clinical practice.
Area of Science:
- Pharmacogenomics
- Pediatric Oncology
- Clinical Implementation Science
Background:
- Interindividual variability in drug response poses challenges in pediatric oncology due to narrow therapeutic windows and combination therapies.
- Pharmacogenetics (PGx) links genetic variants to drug pharmacokinetics, efficacy, and toxicity, aiming to reduce variability.
- Despite available PGx guidelines, pre-emptive screening is not routinely used in pediatric oncology.
Purpose of the Study:
- To describe the implementation strategy for pre-emptive pharmacogenetics (PGx) screening in pediatric oncology in the Netherlands.
- To share insights and address challenges encountered during the integration of PGx screening into routine clinical practice.
- To support other centers in adopting PGx screening for pediatric cancer patients.
Main Methods:
- Repurposed diagnostic germline whole genome sequencing (WGS) for individual genetic profiling.
- Applied existing pharmacogenetic guidelines to interpret results and guide drug dosing and treatment decisions.
- Addressed implementation challenges including infrastructure, result interpretation for pediatrics, EHR integration, and staff education.
Main Results:
- A previous study showed 16% of 1,151 pediatric patients were eligible for genotype-based drug dose or treatment modifications.
- Successfully implemented pre-emptive PGx screening into clinical practice in a Dutch pediatric oncology setting.
- Identified key challenges and developed strategies for successful integration into routine care.
Conclusions:
- Pre-emptive PGx screening is relevant for optimizing drug therapy in pediatric oncology.
- Successful implementation requires addressing infrastructure, interpretation, EHR integration, and education.
- The described strategy and insights can guide other centers in integrating PGx screening into pediatric oncology care.
Related Concept Videos
01:29Pharmacogenetics and Pharmacogenomics: Overview
Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism
In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses a challenge in...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
01:17Pharmacokinetics in Pediatric Patients: Drug Distribution
Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight, compared...
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...