We have first obtained the X-ray crystal structure of the hTS:FdUMP:RTX ternary complex; then, we have investigated the mechanistic features of the synergistic inhibition of the recombinant enzyme by the two compounds; finally, we have explored the efficacy of combinations of RTX and 5FU administered to a panel of ovarian cancer cell lines according to different sequences and have characterized the combination patterns. This evidence concerns the gene APCDD1 and ovarian carcinoma.