This is a real-world medical entrance exam question, please give the true answer based on the question and selection. Topic name: Anti-Neoplastic Agents, Subject name: Pharmacology
[{'content': 'Resistance to Methotrexate develops due to? \nSelect and explain. \nA. Rapid Cancer cell multiplication, B. Deficiency of thymidylate kinase, C. Deficiency of thymidylate synthetase, D. Increased production of dihydrofolate reductase', 'role': 'user'}, {'content': "Answer: D \nExplanation: Ans. is 'd' i.e., Increased production of dihydrofolate reductase Methotrexate resistanceo Methotrexate resistance may be due to any of the following mechanismDefective transport into cellsProduction of altered form ofDHFR that have decreased affinity for methotrexateIncreased concentrations of intracellular DHFR through gene amplification or altered gene regulationDecreased ability to synthesize methotrexate polyglutamatesIncreased expression o f a drug efflux transporter of the MRP (multidrug resistance protein) classDrugMost common mechanism of resistanceo Beta lactamsInactivating enzyme (Beta lactamase)o TetracyclinesEfflux pump (decreased concentration in the cell)o ChloramphenicolInactivating enzyme (acetyl transferase)o MacralidesDecreased permeability or efflux pumpo FluoroquinolonesAltered DNA gyrase with reduced affinityo AminoglycosidesInactivating enzyme", 'role': 'assistant'}]