Pan-RAF inhibitor LY3009120 is highly synergistic with low-dose cytarabine, but not azacitidine, in acute myeloid leukemia with RAS mutations.

ABSTRACT: Alterations in RAS oncogenes have been implicated in various types of cancer, including acute myeloid leukemia (AML). Considering that currently, there are no targeted therapies for patients with RAS-mutated AML despite the poor outcomes, RAF may be a potential target for AML. In this study, we first analyzed the efficacy of different MAPK inhibitors in AML cell lines. We found that LY3009120, a pan-RAF inhibitor, significantly decreased cell survival in RAS-mutated AML cell lines. We then investigated the synergistic effects of LY3009120 with either cytarabine or azacitidine. We found that the combination of low-dose cytarabine and LY3009120 showed a synergistic effect in NRAS-mutated HL-60 cells and KRAS-mutated NB4 cells. This effect was caused by a de

SUBMITTER: Park J 

PROVIDER: S-EPMC8436357 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature