*2.5. Tankyrase Inhibition*

Resistance to PI3/AktT inhibitors is linked to Wnt/b-catenin signaling hyperactivation [103] and can be countered by the Wnt/tankyrase inhibitor NVP-TNKS656 [104]. Hence a direct synergy between tankyrase inhibitors (TNKSi) and OVs might be possible. Tankyrases play a role in the replication of different herpes viruses. The inhibition of tankyrase has been shown to promote replication of beta- (cytomegalovirus) and gammaherpesvirus (Epstein-Barr virus), with the underlying mechanism via which this benefits the virus still to be elucidated [105,106]. In contrast, TNKS inhibition acts suppressive on the alpha-herpesvirus, HSV-1 [104]. However, direct combination regimens of TNKSi and OVs have not yet been published, but such studies might be merited.
