TYMS and neoplasm: To determine whether this innate resistance is indeed dependent on lysosomal sequestration of the drug, the correlation of the lysosome number in the above tumor cell lines was also compared to the cytotoxic activity of two widely used anticancer drugs that do not undergo lysosomal sequestration, the fluoropyrimidine 5-fluorouracil (5-FU), and the antifolate pemetrexed (PMX), both of which inhibit thymidylate synthase, a key enzyme in pyrimidine nucleotide biosynthesis (Fig. 2B and 2C, respectively).