Dual inhibition of BRAF and mTOR in BRAFV600E -mutant pediatric, adolescent, and young adult brain tumors. Cold Spring Harb Mol Case Stud 2020 Aug;6(4)
Date
08/28/2020Pubmed ID
32843426Pubmed Central ID
PMC7476413DOI
10.1101/mcs.a005041Scopus ID
2-s2.0-85089926147 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
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.
Author List
Sen S, Tanaka R, Khatua S, Zaky W, Janku F, Penas-Prado M, Weathers SP, Behrang A, Roszik J, Subbiah VAuthor
Ryuma Tanaka MD Assistant Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Brain Neoplasms
Child
Drug Resistance, Neoplasm
Everolimus
Humans
Mutation
Protein Kinase Inhibitors
Proto-Oncogene Proteins B-raf
TOR Serine-Threonine Kinases
Young Adult
