Langenau David M, Sweet-Cordero Alejandro, Wechsler-Reya Robert, Dyer Michael A
Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02129.
Harvard Stem Cell Institute, Cambridge MA 02139.
Cancer Res. 2015 Dec 15;75(24):5176-5186. doi: 10.1158/0008-5472.CAN-15-1308. Epub 2015 Dec 1.
Despite improvements in survival rates for children with cancer since the 1960s, progress for many pediatric malignancies has slowed over the past two decades. With the recent advances in our understanding of the genomic landscape of pediatric cancer, there is now enthusiasm for individualized cancer therapy based on genomic profiling of patients' tumors. However, several obstacles to effective personalized cancer therapy remain. For example, relatively little data from prospective clinical trials demonstrate the selective efficacy of molecular-targeted therapeutics based on somatic mutations in the patient's tumor. In this commentary, we discuss recent advances in preclinical testing for pediatric cancer and provide recommendations for providing scientific justification and translational relevance for novel therapeutic combinations for childhood cancer. Establishing rigorous criteria for defining and validating druggable mutations will be essential for the success of ongoing and future clinical genomic trials for pediatric malignancies.
尽管自20世纪60年代以来儿童癌症的生存率有所提高，但在过去二十年中，许多儿科恶性肿瘤的进展已经放缓。随着我们对儿科癌症基因组格局理解的最新进展，现在人们热衷于基于患者肿瘤的基因组分析进行个体化癌症治疗。然而，有效的个性化癌症治疗仍存在几个障碍。例如，来自前瞻性临床试验的数据相对较少，无法证明基于患者肿瘤体细胞突变的分子靶向治疗的选择性疗效。在这篇评论中，我们讨论了儿科癌症临床前测试的最新进展，并为为儿童癌症的新型治疗组合提供科学依据和转化相关性提供建议。建立严格的标准来定义和验证可药物化突变对于正在进行的和未来的儿科恶性肿瘤临床基因组试验的成功至关重要。
