Timing is everything: Misincorporation of 8oxodg during mitosis is lethal

Abstract

Exploiting universal cancer vulnerabilities has been used as an approach for developing targeted therapies. In this issue of Cancer Research, Rudd and colleagues show that the dual-functioning inhibitor TH588 potentiates the accumulation of reactive oxygen species during mitosis in cancer by disturbing mitotic progression and simultaneously inhibiting the hydrolysis of 8oxodGTP. This leads to increased incorporation of 8oxodG into the DNA during mitotic replication and increased toxicity. Understanding the mechanism of this inhibitor lays the groundwork for identifying cancer targets.