Insulin feedback is a targetable resistance mechanism of PI3K inhibition in glioblastoma.

ABSTRACT:

Background

Insulin feedback is a critical mechanism responsible for the poor clinical efficacy of phosphatidylinositol 3-kinase (PI3K) inhibition in cancer, and hyperglycemia is an independent factor associated with poor prognosis in glioblastoma (GBM). We investigated combination anti-hyperglycemic therapy in a mouse model of GBM and evaluated the association of glycemic control in clinical trial data from patients with GBM.

Methods

The effect of the anti-hyperglycemic regimens, metformin and the ketogenic diet, was evaluated in combination with PI3K inhibition in patient-derived GBM cells and in an orthotopic GBM mouse model. Insulin feedback and the immune microenvironment were retrospectively evaluated in blood and tumor tissue from a Phase 2 clinical trial of buparlisib

SUBMITTER: Noch EK 

PROVIDER: S-EPMC10708938 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature