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.
Original language | English (US) |
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Article number | a005041 |
Journal | Cold Spring Harbor Molecular Case Studies |
Volume | 6 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2020 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Genetics
- Genetics(clinical)