Abstract TS2-1: The complexity of targeting PI3K for cancer therapy

Phosphoinositide 3-Kinase (PI3K) is activated by insulin and other growth factors to mediate cell growth. The PI3K enzyme encoded by the PIK3CA gene is one of the most frequently mutated oncogenes in human cancer. This same enzyme mediates insulin responses in liver, muscle, fat and other tissues. The most common mutations in this gene enhance the ability of PI3K to be activated by insulin. Since breast cancers typically express relatively high levels of the insulin receptor, high serum insulin levels are likely to enhance activation of PI3K in breast cancers. PI3K inhibitors that target PIK3CA have the expected physiological effect of raising serum glucose and insulin levels and the elevated insulin is likely to compromise the effectiveness of therapy. Data will be presented showing that in mouse models of human breast cancers and other cancers, dietary interventions and pharmaceutical interventions that limit elevation of serum insulin during PI3K therapy improve responses to PI3K inhibitors. Citation Format: Cantley L. The complexity of targeting PI3K for cancer therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr TS2-1.