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2006
Qing-Bai She, Ph.D.
Memorial Sloan-Kettering Cancer Center
Development of Therapeutic Strategies for the Inhibition of PI3K/Akt Kinase-Mediated Signaling Pathways in Glioblastoma
Glioblastoma multiforme (GBM) is characterized by mutations in genes that encoded key regulators of the P13K signaling pathway, including genetic mutations inEGFR, p110? PI3K and PTEN. Inhibition of the PI3K/AKT signaling pathway therefore appears to be a rational therapeutic strategy for this dire disease and preliminary data suggest that inhibitors of PI3K or AKT could be an effective for the treatment of GBM.
Through this grant, Dr. She proposes to study the effects of novel PI3K and AKT inhibitors on the biology of GBM, in tissue culture and animal models, and pursue their preclinical development. They plan to study the pharmacodynamic, biologic and antitumor activity of three novel PI3K and two novel Akt inhibitors in xenograft and transgenic models of GBM. The activity of these agents alone and, based on preliminary data, in combination with temozolomide or EGFR, MEK or mTOR inhibitors will also be studied.
The overall goal of this project is to develop a rational strategy for clinical development of PI3K or Akt in the treatment of GBM, specifically for the majority of tumor subtypes that are unresponsive to single-agent therapy with an EGFR inhibitor.
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