Progress Toward Epigenetic Targeted Therapies for Childhood Cancer.

Among the most significant discoveries from cancer genomics efforts has been the critical role of epigenetic dysregulation in cancer development and progression. Studies across diverse cancer types have revealed frequent mutations in genes encoding epigenetic regulators, alterations in DNA methylation and histone modifications, and a dramatic reorganization of chromatin structure. Epigenetic changes are especially relevant to pediatric cancers, which are often characterized by a low rate of genetic mutations. The inherent reversibility of epigenetic lesions has led to an intense interest in the development of epigenetic targeted therapies. Additionally, the recent appreciation of the interplay between the epigenome and immune regulation has sparked interest in combination therapies and synergistic immunotherapy approaches. Further, the recent appreciation of epigenetic variability as a driving force in cancer evolution has suggested new roles for epigenetic therapies in limiting plasticity and resistance. Here, we review recent progress and emerging directions in the development of epigenetic targeted therapeutics and their promise across the landscape of childhood cancers.