Our results are consistent with the increased potency of CF10 relative to 5-FU and TFT in human and mouse CRC cells resulting from increased replication stress with ATR/Chk1 and ATM/Chk2 DNA damage response pathways activated to counter the deleterious consequences of CF10-induced Top1cc and replication fork collapse resulting in apoptosis, although the non-apoptotic cell death processes may be stimulated by CF10/LV since increased potency correlates with reduced apoptosis. The gene discussed is CHEK2; the disease is colorectal carcinoma.