Pediatric low-grade glioma models: advances and ongoing challenges

Abstract

Pediatric low-grade gliomas represent the most common childhood brain tumor class. While often curable, some tumors fail to respond and even successful treatments can have life-long side effects. Many clinical trials are underway for pediatric low-grade gliomas. However, these trials are expensive and challenging to organize due to the heterogeneity of patients and subtypes. Advances in sequencing technologies are helping to mitigate this by revealing the molecular landscapes of mutations in pediatric low-grade glioma. Functionalizing these mutations in the form of preclinical models is the next step in both understanding the disease mechanisms as well as for testing therapeutics. However, such models are often more difficult to generate due to their less proliferative nature, and the heterogeneity of tumor microenvironments, cell(s)-of-origin, and genetic alterations. In this review, we discuss the molecular and genetic alterations and the various preclinical models generated for the different types of pediatric low-grade gliomas. We examined the different preclinical models for pediatric low-grade gliomas, summarizing the scientific advances made to the field and therapeutic implications. We also discuss the advantages and limitations of the various models. This review highlights the importance of preclinical models for pediatric low-grade gliomas while noting the challenges and future directions of these models to improve therapeutic outcomes of pediatric low-grade gliomas.

Visual Deficits and Diagnostic and Therapeutic Strategies for Neurofibromatosis Type 1: Bridging Science and Patient-Centered Care

“…Additional mouse lines have been developed that more closely resemble NF1 human pathology by introducing human GFAP ( hGFAP-Cre; Nf1 flox/mut ) [ 187 ]. This line exhibited complete penetrance of glial hyperplasia and enlarged optic nerves with lesions that in some cases progressed to form optic pathway gliomas [ 188 ]. Other mouse models achieve OPG formation by activating the KRAS oncogene in astrocytes of heterozygous Nf1 mice [ 189 ], or inhibiting Nf1 in neuroglial progenitors (such as BLBP and Oligo2 [ 190 , 191 ]) thereby increasing proliferation of cells with glial lineage and inducing abnormal neuronal differentiation.…”