Pediatric brain tumors are the second most common malignancy of childhood after acute leukemia and the number one cause of cancer-related mortality¹. Over the past decade, advanced molecular diagnostics have led to the discovery of new molecularly-defined tumor types with prognostic and therapeutic implications. Methylation profiles, whole genome sequencing, and transcriptomics have defined subgroups and revealed heterogeneity within commonly defined tumor entities^2,3. These findings have also revealed important differences between adult and pediatric brain tumors of similar histology. The majority of pediatric low grade gliomas (pLGG) are defined by alterations in the mitogen-activated protein kinase (MAPK) pathway including BRAFV600E point mutation, K1AA1549-BRAF fusion, and FGFR1 alterations as opposed to IDH1/2 mutations and 1p/19q co-deletion seen more frequently in adult low grade gliomas⁴. These findings have led to targeted therapies, namely BRAF and MEK inhibitors, which are currently being evaluated in phase III clinical trials and may soon supplant chemotherapy as standard of care for pLGG's. While targeted therapy trials for pediatric brain tumors have had significant success, immunotherapy remains a challenge in a group of tumors with generally lower mutational burden compared to adult tumors and relatively “cold” immune microenvironment. Despite this, a wide array of immunotherapy trials including vaccine therapies, immune checkpoint blockade, chimeric antigen receptor (CAR) T cells, and viral therapies are on-going. Unique to pediatrics, multiple clinical trials have sought to answer the question of whether the most malignant pediatric brain tumors in the youngest patients can be successfully treated with high dose chemotherapy in lieu of radiation to avoid devastating long-term neurocognitive deficits. Due to the collaborative work of multiple pediatric neuro-oncology consortiums, the recent history of pediatric brain tumor research is one of efficient translation from bench to bedside in a rare group of tumors resulting in significant progress in the field. Here, advances in the areas of molecular characterization, targeted and immune-based therapies, and reduction in long term co-morbidities will be reviewed.

小儿脑肿瘤是仅次于急性白血病的第二大儿童恶性肿瘤，也是导致癌症相关死亡的^第一大原因¹。在过去的十年中，先进的分子诊断导致发现了具有预后和治疗意义的新的分子定义的肿瘤类型。甲基化谱、全基因组测序和转录组学已经定义了亚组并揭示了通常定义的肿瘤实体内的异质性^{2 , 3}. 这些发现还揭示了类似组织学的成人和儿童脑肿瘤之间的重要差异。大多数儿科低级别胶质瘤 (pLGG) 由丝裂原活化蛋白激酶 (MAPK) 通路的改变定义，包括 BRAFV600E 点突变、K1AA1549-BRAF 融合和FGFR1改变，而不是IDH1/2突变和 1p/19q co - 缺失更常见于成人低级别胶质瘤⁴. 这些发现导致了靶向治疗，即 BRAF 和 MEK 抑制剂，目前正在 III 期临床试验中对其进行评估，并且可能很快取代化学疗法作为 pLGG 的标准治疗。虽然针对小儿脑肿瘤的靶向治疗试验取得了重大成功，但免疫治疗在一组与成人肿瘤相比突变负荷普遍较低且免疫微环境相对“冷”的肿瘤中仍然是一个挑战。尽管如此，包括疫苗疗法、免疫检查点阻断、嵌合抗原受体 (CAR) T 细胞和病毒疗法在内的一系列免疫疗法试验仍在进行中。儿科独有，多项临床试验试图回答以下问题：是否可以用高剂量化疗代替放疗成功治疗最年轻患者中最恶性的儿科脑肿瘤，以避免破坏性的长期神经认知缺陷。由于多个儿科神经肿瘤学联盟的合作，儿科脑肿瘤研究的近期历史是在罕见的一组肿瘤中从工作台到床边的有效转化之一，从而在该领域取得了重大进展。在这里，将回顾分子表征、靶向和免疫疗法以及减少长期合并症等领域的进展。儿科脑肿瘤研究的近期历史是在一组罕见的肿瘤中从工作台到床边的有效转化，导致该领域取得重大进展。在这里，将回顾分子表征、靶向和免疫疗法以及减少长期合并症等领域的进展。儿科脑肿瘤研究的近期历史是在一组罕见的肿瘤中从工作台到床边的有效转化，导致该领域取得重大进展。在这里，将回顾分子表征、靶向和免疫疗法以及减少长期合并症等领域的进展。