Childhood Malignant Brain Tumors: Balancing the Bench and Bedside

SIMPLE SUMMARY: Brain tumors remain the most common childhood solid tumors, accounting for approximately 25% of all pediatric cancers. They also represent the most common cause of cancer-related illness and death in this age group. Recent years have witnessed an evolution in our understanding of the biological underpinnings of many childhood brain tumors, potentially improving survival through both improved risk group allocation for patients to provide appropriate treatment intensity, and novel therapeutic breakthroughs. This review aims to summarize the molecular landscape, current trial-based standards of care, novel treatments being explored and future challenges for the three most common childhood malignant brain tumors—medulloblastomas, high-grade gliomas and ependymomas. ABSTRACT: Brain tumors are the leading cause of childhood cancer deaths in developed countries. They also represent the most common solid tumor in this age group, accounting for approximately one-quarter of all pediatric cancers. Developments in neuro-imaging, neurosurgical techniques, adjuvant therapy and supportive care have improved survival rates for certain tumors, allowing a future focus on optimizing cure, whilst minimizing long-term adverse effects. Recent times have witnessed a rapid evolution in the molecular characterization of several of the common pediatric brain tumors, allowing unique clinical and biological patient subgroups to be identified. However, a resulting paradigm shift in both translational therapy and subsequent survival for many of these tumors remains elusive, while recurrence remains a great clinical challenge. This review will provide an insight into the key molecular developments and global co-operative trial results for the most common malignant pediatric brain tumors (medulloblastoma, high-grade gliomas and ependymoma), highlighting potential future directions for management, including novel therapeutic options, and critical challenges that remain unsolved.