Preclinical Evaluation of the Efficacy of the Cyclin-Dependent Kinase Inhibitor Ribociclib in Combination with Letrozole against Patient-Derived Glioblastoma Cells.

ABSTRACT: Ongoing studies suggest that letrozole (LTZ), a drug used in the treatment of breast cancer, can potentially be repurposed as a novel therapeutic for glioblastoma (GBM). In a phase 0/I trial in patients with recurrent GBM, we observed that LTZ permeates into the GBM tissue and triggers dose-dependent changes in the expression of genes regulating the cell cycle [e.g., cyclin-dependent kinase (CDK) inhibitor 2A/2B, CDK4]. Based on these observations, we hypothesized that a combination of CDK4/6 inhibitors and LTZ may result in synergistic anti-GBM activity. Therefore, we assessed the antitumor effects of LTZ in combination with ribociclib, a third-generation CDK4/6inhibitor, and the brain pharmacokinetics of ribociclib. Using cell viability and neurosphere growth assays against a panel of pa

SUBMITTER: Gadgil SN 

PROVIDER: S-EPMC12664761 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature