DHFR and neoplasm: After being delivered in tumor cells, MTX and its derivatives (methotrexate polyglutamate, MTXPG) inhibited the activities of dihydrofolate reductase (DHFR), aminoimidazole carboxamide adenosine ribonucleotide transformylase (ATIC), and thymidylate synthase (TYMS) to interfere one‐carbon metabolism, de novo purine, and pyrimidine synthesis, respectively (Figure 1).