NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap(4)A) and Down-Regulates Immune Response and Cancer Promotion Genes

Marriott, Andrew S.; Vasieva, Olga; Fang, Yongxiang; Copeland, Nikki A.; McLennan, Alexander G.; Jones, Nigel J.

Regardless of the mechanisms where by Ap 4 A exerts its effects and whether these are all physiologically relevant, the practical significance of inhibiting NUDT2 is evident. Our results expand upon the earlier demonstration that NUDT2 promotes proliferation of breast carcinoma cells and that NUDT2 status could be a useful prognostic marker [78] . The potential of NUDT2 as a pleiotropic therapeutic target for cancer simultaneously affecting metastasis, invasion, apoptosis, immunosuppression and inflammation certainly warrants further investigation and validation in different cancer cells and animal models. There are currently no known specific small molecule inhibitors of NUDT2; however such molecules have been described for the related nudix hydrolase MTH1 [174, 175] , suggesting that specific inhibition of NUDT2 may be feasible. It could also be targeted with biotherapeutics. The extent to which the changes in the expression of other genes and pathways brought about by NUDT2 disruption might militate against its value as a target will only be determined by further investigation.