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Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma

Genes encoding TRK are oncogenic drivers in multiple tumour types including infantile fibrosarcoma, papillary thyroid cancer and high-grade gliomas (HGG). TRK fusions have a critical role in tumourigenesis in 40% of infant HGG. Here we report the first case of a TRK fusion-driven HGG treated with la...

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Detalles Bibliográficos
Autores principales: Ziegler, David S., Wong, Marie, Mayoh, Chelsea, Kumar, Amit, Tsoli, Maria, Mould, Emily, Tyrrell, Vanessa, Khuong-Quang, Dong-Anh, Pinese, Mark, Gayevskiy, Velimir, Cohn, Richard J., Lau, Loretta M. S., Reynolds, Mark, Cox, Michael C., Gifford, Andrew, Rodriguez, Michael, Cowley, Mark J., Ekert, Paul G., Marshall, Glenn M., Haber, Michelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173734/
https://www.ncbi.nlm.nih.gov/pubmed/30220707
http://dx.doi.org/10.1038/s41416-018-0251-2
Descripción
Sumario:Genes encoding TRK are oncogenic drivers in multiple tumour types including infantile fibrosarcoma, papillary thyroid cancer and high-grade gliomas (HGG). TRK fusions have a critical role in tumourigenesis in 40% of infant HGG. Here we report the first case of a TRK fusion-driven HGG treated with larotrectinib—the first selective pan-TRK inhibitor in clinical development. This 3-year-old girl had failed multiple therapies including chemotherapy and radiotherapy. Tumour profiling confirmed an ETV6–NTRK3 fusion. Treatment with larotrectinib led to rapid clinical improvement with near total resolution of primary and metastatic lesions on MRI imaging. This is the first report of a TRK fusion glioma successfully treated with a TRK inhibitor.