Department of Pediatrics and Medicine, and Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, Illinois 60637, USA.
Clin Cancer Res. 2012 May 15;18(10):2791-800. doi: 10.1158/1078-0432.CCR-11-1938.
The amazing successes in cure rates for children with cancer over the last century have come in large part from identifying clinical, genetic, and molecular variables associated with response to therapy in large cooperative clinical trials and stratifying therapies according to the predicted risk of relapse. There is an expanding interest in identifying germline genomic variants, as opposed to genetic variants within the tumor, that are associated with susceptibility to toxicity and for risk of relapse. This review highlights the most important germline pharmacogenetic and pharmacogenomic studies in pediatric oncology. Incorporating germline genomics into risk-adapted therapies will likely lead to safer and more effective treatments for children with cancer.
上个世纪,儿童癌症治愈率的惊人提高在很大程度上来自于在大型合作临床试验中确定与治疗反应相关的临床、遗传和分子变量,并根据复发风险对治疗进行分层。人们越来越关注识别与毒性易感性和复发风险相关的种系基因组变异,而不是肿瘤内的遗传变异。这篇综述强调了儿科肿瘤学中最重要的种系药物遗传学和药物基因组学研究。将种系基因组学纳入风险适应性治疗可能会为癌症儿童带来更安全、更有效的治疗方法。