The component of cell death produced by TS inhibition is abnormal uracil incorporation into DNA resulting from build-up of the cytotoxic nucleotide intermediate dUTP and the dUTP pools accumulate. DNA polymerases use dUTP in place of TTP during DNA synthesis and activating repeated rounds of uracil repair due to continue dTTP depletion, resulting in extensive DNA damage and cell death. The enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase), encoded by the DUT gene, which hydrolysing dUTP to dUMP, thereby eliminating dUTP from the DNA biosynthetic pathway. Even though the depletion of dTMP and the accumulation of dUMP is common in cancer cell lines undergoing TS inhibition ,the ability to accumulate dUTP varies definitely. The dUTPase could protect colorectal and breast cancer cells from cytotoxicity induced from dUTP pool expansion and subsequent uracil misincorporation into DNA induced during TS inhibition. Also dUTPase over expression in tumour specimens is associated with resistance to 5-FU in colorectal cancer but numerous solid tumours over express dUTPase, cancel the potential for dUTP pool expansion and cytotoxicity induced by the uracil-DNA misincorporation pathway. After all, if dUTPase activity could be blocked in the presence of TS inhibition and the combined cytotoxicity from concomitant TTP pool depletion, along with uracil misincorporation would result in enhanced DNA damage and cell death.