Thursday, April 18, 2013
Figure 1. Targeting tankyrase to treat
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.