期刊
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
卷 30, 期 11, 页码 831-849出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPH.0b013e3181868570
关键词
pharmacogenetics; childhood acute lymphoblastic leukemia; chemotherapeutic therapy; individualized treatment
资金
- Ministry of Health [2006-12103-250]
- Novo Nordisk Foundation, Danish Cancer Council for Health and Disease [271-06-0278]
- Danish Childhood Cancer Foundation
Pharmacogenetics covers the genetic variation affecting pharmacokinetics and pharmacodynamics. and their influence on drug-response phenotypes. The genetic variation includes an estimated 15 million single nucleotide polymorphisms (SNP) and is a key determinator for the interindividual differences in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far Focus has mainly been on the widely used glucocorticosteroids, methotrexate. and thiopurines, or on metabolic pathways and transport mechanisms that are common to Several drugs, Such as the glutathione S-transferases. However, beyond the thiopurine methyltransferase polymorphisms, the candidate-gene approach has not established clear associations between polymorphisms treatment response. In the future, high-throughput, low-cost, genetic platforms will allow screening of hundreds or thousands of targeted SNPs to give a combined gene-dosage effect ( = individual SNP risk profile), which may allow pharmacogenetic-based individualization of treatment.
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