PI3K Signaling Pathway Activation Predicts Class I PI3K Inhibitor GDC-0941 Sensitivity in AML.

Abstract 1057 Poster Board I-79 The PI3K-Akt signal transduction pathway plays a key role in the pathogenesis of many human cancers. In AML malignancy, deregulation of upstream receptor tyrosine kinases such as FLT3, c-Kit, and c-FMS or mutations in K-Ras, N-Ras, B-Raf and CEBPA genes lead to activation of PI3K-Akt signaling to promote cell survival and cell growth. A highly selective Class I PI3K inhibitor, GDC-0941, provides exciting therapeutic opportunities for targeting this pathway in AML. Here we show that GDC-0941 significantly inhibits the viability of the majority of a large panel of AML cell lines tested in vitro (80% or 19/24) at a concentration of 2 cell cycle arrest. Together, our preclinical data suggest that GDC-0941 may be used as a targeted therapy in AML patients as a single agent or in combination with other chemotherapies in clinic. Disclosures: Ma: Genentech Inc.: Employment. Du: Genentech, Inc.: Employment, Equity Ownership. Sun: Genentech Inc.: Employment. Shi: Genentech, Inc.: Employment, Equity Ownership. Friedman: Genentech Inc.: Employment. Dornan: Genentech, Inc.: Employment, Equity Ownership. Ebens: Genentech, Inc.: Employment, Equity Ownership, Patents & Royalties.