Methotrexate resistance is due to
Mechanism for Methotrexate resistance Impaired transpo of Methotrexate into cells Production big altered forms of DHFR that have decreased affinity for the inhibitor Increased concentrations of intracellular DHFR through gene amplification Decreased ability to synthesize Methotrexate polyglutamtes Increased expression of a drug reflux transpoer, of MRP class Refer Goodman Gilman 11/e p1336
Depletion of folate
Overproduction of DHFRase
Overproduction of thymidylate kinase
Decreased DHFR ase
Chemotherapy