DHFR and cancer: The search was based on a preliminary forecast of the probability of antitumor activity for 8 mechanisms, including alkylating action (Alk), antimitotics (AMi), inhibitors of topoisomerase 1 (TI-1), topoisomerase 2 (TI-2), dihydrofolate reductase (DHFR), DNA—antimetabolites (cancer DNA, or cDNA), cyclin-dependent kinase (CDK4), and epidermal growth factor receptor (EGFR).