Role of MTH1 in oxidative stress and therapeutic targeting of cancer

Summary

Cancer cells maintain high levels of reactive oxygen species (ROS) to drive their growth, but ROS can trigger cell death through oxidative stress and DNA damage. To survive enhanced ROS levels, cancer cells activate their antioxidant defenses. One such defense is MTH1, an enzyme that prevents the incorporation of oxidized nucleotides into DNA, thus preventing DNA damage and allowing cancer to proliferate. MTH1 levels are often elevated in many cancers, and thus, inhibiting MTH1 is an attractive strategy for suppressing tumor growth and metastasis. Targeted MTH1 inhibition can induce DNA damage in cancer cells, exploiting their vulnerability to oxidative stress and selectively targeting them for destruction. Targeting MTH1 is promising for cancer treatment because normal cells have lower RO