DHFR and cancer: Several investigators have demonstrated that the anti-cancer methotrexate (MTX) and trimetrexate (TMX), which are inhibitors of dihydrofolate reductase (DHFR), are potent against both pyrimethamine (PM) sensitive and PM-resistant P. falciparum strains (parasites harboring wild type or mutant dhfr respectively), including those carrying the Ileu-164-Leu dhfr codon, with IC50 < 85 nM (inhibitory concentration that kill 50% of parasitaemia) [6-10].