Methotrexate resistance is due to:
Ans. (B) Overproduction of DHFRase(Ref: Goodman and Gilman, 11th/e p1336)Mechanisms of methotrexate resistanceImpaired transport of methotrexate into cellsProduction of altered forms of DHFR that have decreased affinity for the inhibitorIncreased concentrations of intracellular DHFR through gene amplification or altered gene regulationDecreased ability to synthesize methotrexate polyglutamatesIncreased expression of a drug efflux transporter, of the MRP (multidrug resistance protein) class.
Depletion of folate
Overproduction of DHFRase
Overproduction of thymidylate kinase
Decreased DHFRase
Chemotherapy: General Principles