Dr. Haura’s research focuses on tyrosine kinase signaling pathways and biomarkers in lung cancer. His group demonstrated activity of SRC kinase inhibitors in lung cancer cells with activating EGFR mutations (Song et al, Cancer Res, 2006); subsequently they reported a strategy to comprehend signaling pathways active in lung cancer cells and targeted by dasatinib employing chemical proteomics to identify direct interacting proteins combined with immunoaffinity purification of tyrosine phosphorylated peptides corresponding to activated tyrosine kinases. They identified nearly 40 different kinase targets of dasatinib, including SFK members (LYN, SRC, FYN, LCK, YES), non-receptor tyrosine kinases (FRK, BRK, ACK), and receptor tyrosine kinases (ephrin receptors, DDR1, EGFR). Using drug resistant gatekeeper mutants, they showed that SFK kinases, particularly SRC and FYN as well as EGFR, are relevant targets for dasatinib action. The combined mass spectrometry-based approach provides a system-level view of dasatinib action in cancer cells and suggests both functional targets and rationale combinatorial therapeutic strategies. A phase I trial of the EGFR inhibitor erlotinib in combination with dasatinib was performed; side effects of the combination were tolerable, disease control and inhibition of plasma angiogenesis markers were observed, and two partial responses and one bone response were observed. Reductions in plasma VEGF and bFGF were observed, and reductions in VEGF correlated with disease control (supported by P50 CA119997). Future directions involve using protein-protein interaction mapping to define novel targets and biomarkers of kinase inhibitors.