Saletta Federica, Wadham Carol, Ziegler David S, Marshall Glenn M, Haber Michelle, McCowage Geoffrey, Norris Murray D, Byrne Jennifer A
Children's Cancer Research Unit, Kids Research Institute, Westmead 2145, New South Wales, Australia.
Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick 2031, New South Wales, Australia.
BBA Clin. 2014 Jun 28;1:59-77. doi: 10.1016/j.bbacli.2014.06.003. eCollection 2014 Jun.
Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies.
This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type.
There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies.
The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.
包括高通量测序在内的技术进步已在儿童和青少年癌症中鉴定出众多肿瘤特异性基因变化，这些变化可被用作新型疗法的靶点。
本综述详细概述了针对儿童癌症的靶向特异性疗法作为单一药物或与其他疗法联合应用的最新进展。该综述根据癌症类型总结了临床试验所基于的临床前证据、早期临床试验结果以及预测性生物标志物在临床实践中的纳入情况。
越来越多的证据表明，分子靶向疗法可有效增加治疗儿童癌症的可用手段，特别是与其他疗法联合使用时。然而，将分子靶向药物引入实践仍具有挑战性，原因在于一些临床试验中使用了未经过筛选的人群、评估疗效的方法不足，以及需要改进临床前模型以评估联合疗法的剂量和安全性。
对癌症分子病因异质性的认识不断提高，有利于分子靶向药物的持续开发及其向儿童和青少年人群的转化。
