Methotrexate resistance

Decreased levels of the MTX polyglutamate have been reported in resistant cells and may be due to its decreased formation or increased breakdown. Resistance in neoplastic cells can be due to amplification (production of additional copies) of the gene that codes for DHFR, resulting in increased levels of this enzyme. The enzyme affinity for MTX may also be diminished. Resistance can also occur from a reduced influx of MTX, apparently caused by a change in the carrier-mediated transport responsible for pumping the drug into the cell.