Finally, the therapeutic dNTPs used in our study not only inhibit telomerase, but also inhibit mitochondrial DNA polymerase γ, leading to mitochondrial dysfunction and elevated ROS which damage dNTP pools26,27.Therefore, in conjunction with MTH1 inhibitors, our studies suggest therapeutic NRTIs or thiopurines may deliver a one–two punch to telomerase-driven cancers by inhibiting telomerase directly and indirectly through elevated oxidized dNTPs. This evidence concerns the gene NUDT1 and cancer.