OGG1 inhibition as combination treatment for cancer therapy

Abstract

Novel anticancer therapies are needed to overcome drug resistance of chemotherapeutic drugs leading to tumor relapse. Combination therapy with target-specific drugs underlies great potential to increase the efficiency of chemotherapy. Increased DNA repair capacity is one of the resistance mechanism of chemotherapy drug cisplatin. Here, inhibitors against DNA glycosylase OGG1 were studied to overcome cisplatin resistance. Combination treatment of OGG1 inhibitor with cisplatin reduced the proliferation of cisplatin resistant bladder cancer cells, whereas sensitive cells did not respond. Increased OGG1 levels in resistant cells and decreased OGG1-GEP mobility upon cisplatin treatment suggests that OGG1 might support cisplatin resistance. Moreover, the activity of PGG1 upon MTH1 inhibition was studied as a side project as both of these enzymes are responsible for 8-oxoG repair, but the findings did not support a role of OGG1 in mediating DNA repair upon MTH1 inhibition. Overall, this study gives insights how OGG1 inhibition could be exploited in anticancer combination therapy.