TEK and cancer: (i) We developed, for the first time, non-immunoglobulin multi-specific single domain inhibitors that target all known cancer-promoting functions resulting from Tie2/integrin αvβ3 crosstalk, and (ii) these new inhibitors allowed us to separately explore the role of each signaling molecule (i.e., Tie2 and integrin αvβ3) in cancer cell invasion and angiogenesis.