Abstract MS1-1: Targeting PI3K

Abstract Phosphoinositide 3-Kinase (PI3K) is a central enzyme in a signaling pathway that mediates cellular responses to growth factors. The signaling pathway downstream of PI3K is highly conserved from worms and flies to humans and genetic analysis of the pathway has revealed a conserved role in regulating glucose metabolism and cell growth. Mutational events that lead to hyperactivation of the PI3K pathway result in hamartoma syndromes and cancers. Activating mutations in PIK3CA, encoding the p110alpha catalytic subunit of PI3K (PIK3CA) or inactivating mutations in PTEN, a phosphoinositide 3-phosphatases that reverses the effects of PI3K, are among the most common events in solid tumors, especially breast cancers. Drugs that target PI3K are in clinical trials for a variety of cancers. It is likely that PI3K pathway inhibitors will need to be combined with other drugs to be broadly effective. We have employed genetically engineered mouse models that develop cancers due to mutations in genes in the PI3K pathway and are using these models to explore the efficacy of PI3K pathway inhibitors as single agents or in combination with other drugs. We are also interrogating the role of PI3K in the growth and survival of Brca1/p53 mutant breast cancers. The role of PI3K inhibitors for treating cancers in these mouse models and in human trials will be discussed. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr MS1-1.