Figure 2.

Signaling schematic for ASPS tumors and novel therapeutic targets. (a) Overexpression of the MET tyrosine receptor kinase is induced by the ASPSCR1-TFE3 fusion protein. This leads to intracellular activation of the promitotic growth kinases Akt and MEK1/2; these in turn lead to unchecked cellular proliferation. (b) Targets for novel therapeutics include the VEGF tyrosine kinase receptor and its ligand (Recentin and Avastin, resp.), as well as tumor cell receptor tyrosine kinases (Sutent, Nexavar, and ARQ 197). Perifosine is a unique inhibitor of the Akt kinase.