Dual inhibition of BRAF and mTOR in BRAFV600E -mutant pediatric, adolescent, and young adult brain tumors.
Cold Spring Harb Mol Case Stud
; 6(4)2020 08.
Article
em En
| MEDLINE
| ID: mdl-32843426
ABSTRACT
Although BRAF inhibition has demonstrated activity in BRAFV600 -mutated brain tumors, ultimately these cancers grow resistant to BRAF inhibitor monotherapy. Parallel activation of the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway has been implicated as a mechanism of primary and secondary resistance to BRAF inhibition. Moreover, it has been shown specifically that mTOR signaling activation occurs in BRAF-mutant brain tumors. We therefore conducted phase 1 trials combining vemurafenib with everolimus, enrolling five pediatric and young adults with BRAFV600 -mutated brain tumors. None of the patients required treatment discontinuation as a result of adverse events. Overall, two patients (40%) had a partial response and one (20%) had 12 mo of stable disease as best response. Co-targeting BRAF and mTOR in molecularly selected brain cancers should be further investigated.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Proteínas Proto-Oncogênicas B-raf
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Serina-Treonina Quinases TOR
Limite:
Adolescent
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Adult
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Child
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Humans
Idioma:
En
Revista:
Cold Spring Harb Mol Case Stud
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos