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

Evan K Noch,Laura N Palma,Isaiah Yim,Nayah Bullen, Yuqing Qiu,Hiranmayi Ravichandran,Junbum Kim,Andre Rendeiro,Melissa B Davis,Olivier Elemento,David J Pisapia,Kevin Zhai,H Carl LeKaye, Jason A Koutcher,Patrick Y Wen,Keith L Ligon,Lewis C Cantley

Neuro-oncology（2023）

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摘要

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.

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关键词

glioblastoma, hyperglycemia, insulin, metformin, phosphatidylinositol 3-kinase

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