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.
David H GutmannPublished in: Neuro-oncology advances (2024)
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.
Keyphrases
- low grade
- high grade
- signaling pathway
- pi k akt
- papillary thyroid
- lps induced
- young adults
- oxidative stress
- nuclear factor
- single cell
- squamous cell
- mouse model
- childhood cancer
- cell therapy
- case report
- inflammatory response
- high resolution
- white matter
- lymph node metastasis
- multiple sclerosis
- cell proliferation
- squamous cell carcinoma
- blood brain barrier
- brain injury
- optic nerve