Figure 1.

Rationale for enhancing replication stress to kill cancer cells. DNA replicative stress can be induced by various factors including ROS, insufficient dNTP, oncogene activation or the loss/inactivation of tumor suppressors, etc. At the low to mild level, the replicative stress predominantly induces genomic instability, therefore facilitates tumorigenesis and cancer progression. However, when the replicative stress is enhanced to a high level through further loss of checkpoints, cancer cells may enter the mitotic phase with incomplete or uncorrected DNA replication, which eventually leads to cell death through mitotic catastrophe. Therefore, enhancing replicative stress can be a novel approach to kill cancer cells. TSG: Tumor suppressing gene.