Optimizing preclinical pediatric low-grade glioma models for meaningful clinical translation

• DOI: 10.1093/neuonc/noad125
• Publication Date: 2023-09-22T20:56:01Z
• Authors: Till Milde; Jason Fangusaro; Michael J Fisher; Cynthia Hawkins; Fausto J Rodriguez; Uri Tabori; Olaf Witt; Yuan Zhu; David H Gutmann
• Keywords: Brain tumor

Abstract Pediatric low-grade gliomas (pLGGs) are the most common brain tumor in young children. While they typically associated with good overall survival, children these central nervous system tumors often experience chronic tumor- and therapy-related morbidities. Moreover, individuals unresectable frequently have multiple recurrences persistent neurological symptoms. Deep molecular analyses of pLGGs reveal that caused by genetic alterations converge on a single mitogenic pathway (MEK/ERK), but their growth is heavily influenced nonneoplastic cells (neurons, T cells, microglia) local microenvironment. The interplay between neoplastic cell MEK/ERK activation stromal support necessitates use predictive preclinical models to identify promising drug candidates for clinical evaluation. As part series white papers focused pLGGs, we discuss current status pLGG modeling, goal improving translation tumors.