Figure 3.

Target therapies for ligand-dependent tumors. All ligand-dependent tumors require Wnt ligands for pathway activation and so are sensitive to porcupine inhibitors that impair Wnt ligand activation. RSPO3 overexpression can be antagonized by anti-RSPO3 antibodies. Ligand-dependent GSK3 inhibition results in reduced proteasomal degradation to generate amino acids such as asparagine, making tumor cells sensitive to asparagine depletion with asparaginase treatment. Ligand-dependent tumors are characterized by AXIN2 repression which can be antagonized with licensed demethylating agents such as azacitidine.