Abstract
Neurotrophins and their related tyrosine kinase receptors (TRKs), encoded by the neurotrophic tyrosine receptor kinase genes NTRKs, play a crucial role in central nervous system development. Oncogenic NTRK gene fusion events have been identified in several cancer subtypes and cause constitutive activation of the TRK receptor, promoting tumorigenesis. While NTRK fusions are rare in cancers overall, they have been identified in appreciable frequency in certain CNS tumors subtypes recently. In other non-CNS neoplasms, the development of NTRK fusion directed therapies has been developed with TRK inhibitors showing promise in clinical trials. Given the difficulty in treating certain pediatric CNS tumors such as high grade gliomas, understanding NTRK fusions in pediatric CNS tumors may lead to more directed treatment and subsequent therapeutic benefit. This review examines the biology of NTRK fusions, the frequency and clinical significance in pediatric CNS tumors, and methods for detection of NTRK fusion in CNS tumors.
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