DHFR and cancer: MTX-PG can strongly bind to DHFR and is minimally subject to competition by LV, which results in long-lasting inhibition of DHFR.11–13 Unlike normal cells, tumor cells exhibit frequent occurrence of polyglutamylation.14 Therefore, MTX treatment can selectively kill cancer cells with high levels of polyglutamylation, whereas normal cells with lower levels of polyglutamylation are rescued by LV.15