Clearing the path to Wnt

Despite the clear involvement of the Wnt pathway in cancer,^1,2 there are no disclosed inhibitors of Wnt signaling in the clinic. The reasons are twofold: the pathway is almost entirely intracellular and most of the interactions are protein-protein. Thus, antibodies are a poor option because they do not readily get inside of cells, and small molecules are equally challenging because they are not good at blocking protein-protein interactions.

Now, a team at Novartis AG's Novartis Institutes for Biomedical Research (NIBR) has found two new components of the Wnt pathway-TNKS1 (tankyrase TRF1-interacting ankyrin-related ADP-ribose polymerase) and TNKS2-that could be more druggable because they are enzymes. The company already has small molecule tankyrase inhibitors in early-stage development...