This is a real-world medical entrance exam question, please give the true answer based on the question and selection. Topic name: Chemotherapy, Subject name: Pharmacology
Methotrexate resistance is due to 
Select and explain. 
A. Depletion of folate, B. Overproduction of DHFRase, C. Overproduction of thymidylate kinase, D. Decreased DHFR ase
B: Overproduction of DHFRase
Answer: B: Overproduction of DHFRase 
Explanation: 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