Despite the success of targeted drugs in cancer care, patients frequently develop resistance to these drugs. This may be due to intra-tumor heterogeneity and the existence of genomically diverse cells within a single tumor. In theory, the cells that do not respond to the targeted drug will expand and become the dominant cell population in a tumor. Using a novel experimental and computational approach, we will infer tumor cell ancestry and measure intra-tumor heterogeneity in HER2 positive stomach cancers. We will determine whether intra-tumor heterogeneity predicts response to Herceptin and will identify biomarkers that are associated with treatment resistance.