Nf1-Mutant Tumors Undergo Transcriptome and Kinome Remodeling after Inhibition of either mTOR or MEK.

ABSTRACT: Loss of the tumor suppressor NF1 leads to activation of RAS effector pathways, which are therapeutically targeted by inhibition of mTOR (mTORi) or MEK (MEKi). However, therapeutic inhibition of RAS effectors leads to the development of drug resistance and ultimately disease progression. To investigate molecular signatures in the context of NF1 loss and subsequent acquired drug resistance, we analyzed the exomes, transcriptomes, and kinomes of Nf1-mutant mouse tumor cell lines and derivatives of these lines that acquired resistance to either MEKi or mTORi. Biochemical comparisons of this unique panel of tumor cells, all of which arose in Nf1^+/- mice, indicate that loss of heterozygosity of Nf1 as an initial genetic event does not confer a common

SUBMITTER: Pucciarelli D 

PROVIDER: S-EPMC7907257 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature