Molecular Heterogeneity in BRAF-Mutant Gliomas: Diagnostic, Prognostic, and Therapeutic Implications

Autor: Benoit Lhermitte, Thibaut Wolf, Marie Pierre Chenard, Andres Coca, Julien Todeschi, François Proust, Edouard Hirsch, Roland Schott, Georges Noel, Eric Guerin, Damien Reita, Agathe Chammas, Alexandra Salmon, Sophie Martin, Monique Dontenwill, Natacha Entz-Werlé
Rok vydání: 2023
Předmět:
Zdroj: Cancers. 15:1268
ISSN: 2072-6694
Popis: Over the last few decades, deciphering the alteration of molecular pathways in brain tumors has led to impressive changes in diagnostic refinement. Among the molecular abnormalities triggering and/or driving gliomas, alterations in the MAPK pathway reign supreme in the pediatric population, as it is encountered in almost all low-grade pediatric gliomas. Activating abnormalities in the MAPK pathway are also present in both pediatric and adult high-grade gliomas. Across those alterations, BRAF p.V600E mutations seem to define homogeneous groups of tumors in terms of prognosis. The recent development of small molecules inhibiting this pathway retains the attention of neurooncologists on BRAF-altered tumors, as conventional therapies showed no significant effect, nor prolonged efficiency on the high-grade or low-grade unresectable forms. Nevertheless, tumoral heterogeneity and especially molecular alteration(s) associated with MAPK-pathway abnormalities are not fully understood with respect to how they might lead to the specific dismal prognosis of those gliomas and/or affect their response to targeted therapies. This review is an attempt to provide comprehensive information regarding molecular alterations related to the aggressiveness modulation in BRAF-mutated gliomas and the current knowledge on how to use those targeted therapies in such situations.
Databáze: OpenAIRE
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