期刊
CANCER CELL
卷 9, 期 5, 页码 341-349出版社
CELL PRESS
DOI: 10.1016/j.ccr.2006.03.029
关键词
-
资金
- NCI NIH HHS [P50 CA097257, P50 CA097257-04, P50 CA097257-05] Funding Source: Medline
The P13 kinase family of lipid kinases promotes cell growth and survival by generating the second messenger phosphatidy-linositol-3,4,5-trisphosphate. To define targets critical for cancers driven by activation of P13 kinase, we screened a panel of potent and structurally diverse drug-like molecules that target this enzyme family. Surprisingly, a single agent (PI-103) effected proliferative arrest in glioma cells, despite the ability of many compounds to block P13 kinase signaling through its downstream effector, Akt. The unique cellular activity of PI-103 was traced directly to its ability to inhibit both P13 kinase alpha and mTOR. PI-103 showed significant activity in xenografted tumors with no observable toxicity. These data demonstrate an emergent efficacy due to combinatorial inhibition of mTOR and P13 kinase alpha in malignant glioma.
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