Department of Pediatrics, Centre Mère-Enfant, Centre Hospitalier de l'Université Laval, Québec, Canada.
Centre de Recherche du Centre Hospitalier Universitaire de Québec, Université Laval, Québec, Canada.
Clin Cancer Res. 2017 Sep 15;23(18):5329-5338. doi: 10.1158/1078-0432.CCR-16-0115. Epub 2017 Jun 9.
Survival of children with cancers has dramatically improved over the past several decades. This success has been achieved through improvement of combined modalities in treatment approaches, intensification of cytotoxic chemotherapy for those with high-risk disease, and refinement of risk stratification incorporating novel biologic markers in addition to traditional clinical and histologic features. Advances in cancer genomics have shed important mechanistic insights on disease biology and have identified "driver" genomic alterations, aberrant activation of signaling pathways, and epigenetic modifiers that can be targeted by novel agents. Thus, the recently described genomic and epigenetic landscapes of many childhood cancers have expanded the paradigm of precision medicine in the hopes of improving outcomes while minimizing toxicities. In this review, we will discuss the biologic rationale for molecularly targeted therapies in genomically defined subsets of pediatric leukemias, solid tumors, and brain tumors. .
在过去的几十年中，患有癌症的儿童的生存率有了显著提高。这一成功是通过改进综合治疗方法、对高危疾病患者加强细胞毒性化疗以及在传统临床和组织学特征基础上加入新的生物学标志物来完善风险分层来实现的。癌症基因组学的进步为疾病生物学提供了重要的机制见解，并确定了“驱动”基因组改变、信号通路的异常激活以及可以通过新型药物靶向的表观遗传修饰剂。因此，最近描述的许多儿童癌症的基因组和表观基因组图谱扩展了精准医学的范例，以期在降低毒性的同时提高疗效。在这篇综述中，我们将讨论在基因定义的儿科白血病、实体瘤和脑肿瘤亚组中进行分子靶向治疗的生物学依据。
