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

Evan K NochLaura N PalmaIsaiah YimNayah BullenYuqing QiuHiranmayi RavichandranJunbum KimAndre RendeiroMelissa B DavisOlivier ElementoDavid J PisapiaKevin ZhaiH Carl LeKayeJason A KoutcherPatrick Y WenKeith L LigonLewis C Cantley

Published in: Neuro-oncology (2023)

Reducing insulin feedback improves the efficacy of PI3K inhibition in glioblastoma in mice, and hyperglycemia worsens progression-free survival in patients with glioblastoma treated with PI3K inhibition. These findings indicate that hyperglycemia is a critical resistance mechanism associated with PI3K inhibition in glioblastoma and that anti-hyperglycemic therapy may enhance PI3K inhibitor efficacy in glioblastoma patients.

Keyphrases

type diabetes
free survival
newly diagnosed
ejection fraction
end stage renal disease
stem cells
adipose tissue
glycemic control
oxidative stress
prognostic factors
patient reported outcomes
skeletal muscle
bone marrow
insulin resistance