Effects of combination therapy of a CDK4/6 and MEK inhibitor in diffuse midline glioma preclinical models.

ABSTRACT:

Background

Diffuse midline glioma (DMG) is an incurable brain cancer without a single FDA-approved drug that prolongs survival. CDK4/6 inhibitors have been evaluated in children with DMG with limited efficacy. Since MAPK pathway activation is upstream of cell proliferation, we hypothesized that MEK inhibitors may increase the anti-tumor effects of CDK4/6 inhibitors. Here, we evaluated the efficacy of the CDK4/6 inhibitor ribociclib and the MEK inhibitor trametinib in human and murine DMG models to investigate combinational effects.

Methods

We conducted in vitro and in vivo assays using DMG cell lines from human patient-derived xenografts (PDX) and genetically engineered mouse (GEM) models. In vitro, we assessed synergy across human DMG lines. In vivo, we evaluated therapeuti

SUBMITTER: Tomita Y 

PROVIDER: S-EPMC12721541 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature