Leveraging murine models of the neurofibromatosis type 1 cancer predisposition syndrome to elucidate the cellular circuits that drive pediatric low-grade glioma formation and progression

TL;DR

This paper explores how mouse models of a genetic disorder help understand and treat a common type of childhood brain tumor.

Contribution

The study identifies cell-intrinsic and stromal dependencies in pediatric low-grade gliomas using NF1 mouse models.

Findings

NF1 gene mutations are a hereditary cause of low-grade gliomas in children.

Mouse models reveal MEK signaling and stromal dependencies as potential therapeutic targets.

Targeted agents can be tested in preclinical models before clinical use.

Abstract

Brain tumors are the leading cause of cancer-related death in children, where low-grade gliomas (LGGs) predominate. One common hereditary cause for LGGs involves neurofibromatosis-1 (NF1) gene mutation, as seen in individuals with the NF1 cancer predisposition syndrome. As such, children with NF1 are at increased risk of developing LGGs of the optic pathway, brainstem, cerebellum, and midline brain structures. Using genetically engineered mouse models, studies have revealed both cell-intrinsic (MEK signaling) and stromal dependencies that underlie their formation and growth. Importantly, these dependencies represent vulnerabilities against which targeted agents can be used for preclinical investigation prior to clinical translation.

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