Figure 1. Targeting tankyrase to treat tumors. Lau et al. and Voronkov et al. have shown that small molecule inhibitors of tankyrase TRF1-interacting ankyrin-related ADP-ribose polymerase (TNKS) and TNKS2 can slow the growth of colorectal cancer xenografts in mice.

In colorectal cancer, wingless-type MMTV integration site (WNT) signaling through various frizzled receptors [a] leads to stabilization of b-catenin (CTNNB1), which enters the nucleus [b] and turns on genes that drive tumor proliferation [c].

Lau et al. and Voronkov et al. found that G007-LK [d], a small molecule inhibitor of TNKS and TNKS2 that is licensed to Odin Therapeutics A/S, prevents this series of events. TNKS and TNKS2 cause the degradation of axin proteins, which counteracts the accumulation of CTNNB1. G007-LK treatment leads to stabilization of axins and blocks CTNNB1 activity [e], thus inhibiting tumor growth.