![]() ![]() The mutations usually occur at BRAF in this pathway, including the KIAA1549-BRAF fusion and BRAF V600E mutant, which lead to constitutive activation of the MAPK pathway. The aberrant Ras-mitogen activated protein kinase (MAPK) signaling pathway is mainly reported in LGG. Histologically, LGGs include pilocytic astrocytoma (PA), pilomyxoid astrocytoma (PMA), oligoastrocytoma, subependymal giant cell astrocytoma (SEGA), pleomorphic xanthoastrocytomas (PXA), oligodendroglioma, ganglioglioma, dysembryoplastic neuroepithelial tumors, etc., among which pilocytic astrocytoma is the most common form. ![]() LGG is the most common glioma, which is typically nonmalignant and slow growing. Glioma are highly heterogeneous tumors, ranging from low-grade glioma (LGG) to high-grade glioma (HGG) depending on the tumor malignant status. Glioma can originate from all glia cell types and 75% of these glial tumors are astrocytoma ( 1). ![]() Glioma is the most common pediatric primary brain tumor, representing approximately 47% of brain tumor cases in the age group of 0-19 years. Common Pediatric Brain Tumors and Molecular Subgrouping Gliomas We also discuss the advantages and limitations of each model, which need to be considered when choosing an appropriate tumor model that best suits the experimental purpose. In this review, we provide an overview of the most common pediatric brain tumors and currently available well-annotated in vitro and in vivo tumor models. Brain tumor models that can mimic tumor initiation and progression, and predict a tumor’s response to treatments in vivo are fundamental to achieve this goal. With the overall success rate of new anticancer drugs remaining low ( 7, 8), we will need to switch from “one size fits all” treatments to more specific individualized strategies, to increase treatment efficacy, to reduce complications due to treatment, and to improve the translation rate of anti-cancer drugs. In 2016, the World Health Organization (WHO) updated classification of central nervous system tumors by incorporating molecular features into traditional histological characteristics for more accurate diagnosis, prognosis predictions, and treatments ( 2– 6). In addition, some histologically ambiguous tumors may largely rely on their molecular characterization for their diagnosis and treatment plan. ![]() However, more and more evidence shows that histologically similar brain tumors sometimes have distinct molecular features they respond differently to the treatment and have various prognosis as well. In the past, the diagnosis and classification of brain tumors had largely relied on histological characteristics derived from hematoxylin and eosin-staining, and immunohistochemical detection of lineage-associated proteins. The incidence and mortality rate of primary brain and other central nervous system tumors have not changed significantly in recent years, with an average incidence rate of 5.65 per 100,000 population and an average mortality rate of 0.72 per 100,000 population for the 0 to 14 years age group from 2011 to 2015 in the United States ( 1). Here we give an overview of currently available in vitro and in vivo pediatric brain tumor models and discuss the opportunities that new technologies such as 3D cultures and organoids that can bridge limitations posed by the simplicity of monolayer cultures and the complexity of in vivo models, bring to accommodate better precision in drug development for pediatric brain tumors.īrain tumors are the most common solid tumors and the leading cause of cancer-related death in children. Besides molecularly driven patient stratification to tailor disease risk to therapy intensity, such a diversity demonstrates the need for more precise and disease-relevant pediatric brain cancer models for research and drug development. Even within historically defined tumor types such as medulloblastoma, molecular analysis identified biologically heterogeneous subgroups each with different genetic alterations, age of onset and prognosis. The 5-year survival rates, however, vary widely by tumor type, ranging from over 90% in more benign tumors to as low as 20% in the most aggressive forms such as glioblastoma. Despite advances in treatment, brain tumors remain a leading cause of death in pediatric cancer patients and survivors often suffer from life-long consequences of side effects of therapy. duPont Hospital for Children, Wilmington, DE, United StatesĪfter leukemia, tumors of the brain and spine are the second most common form of cancer in children. Nemours Biomedical Research, Alfred I. ![]()
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