495 The PI3K/mTOR Inhibitor GDC-0980 Demonstrates Target Engagement and Pathway Modulation in Tumor Tissue at Tolerated Doses

colon (14%) and gastric (5%). In contrast, other cancer types favored one pathway almost exclusively and thus had little co-occurrence. For example, breast cancer and lung squamous significantly favored PI3K pathway whereas lung adenocarcinoma favored MAPK pathway. Conclusions: These analyses provide an in depth molecular classification of the MAPK and PI3K pathways in common cancers, revealing considerable heterogeneity across cancer types. These data likely have important ramifications for the development of single-agent and combination therapies targeting these pathways. Furthermore, by identifying additional driver alterations in these pathways, we have expanded the molecular subpopulations that may benefit from targeted pathway agents.