Pre-clinical studies showed that the prototype FP polymer F10 improved antitumor activity relative to 5-FU in multiple tumor models [14,15] through a mechanism involving highly potent TS inhibition and the formation of DNA–protein crosslinks with DNA topoisomerase 1 (Top1), referred to as Top1 cleavage complexes (Top1ccs) [16,17]. This evidence concerns the gene TYMS and neoplasm.