Druggable Mutations in Childhood Cancer

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. Cancer Res; 75(24); 5176–86. ©2015 AACR.

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