A. FOLIC ACID ANALOGUES: METHOTREXATE, PEMETREXED, PRALATREXATE
Resistance
- changes in target enzymes
- production of DHFR with a decreased affinity
- increased DHFR expression
- decreased formation of poly-G/MTX
- decreased drug accumulation due to impaired transport
- due to decreased expression of the reduced folate carrier (either primary or acquired resistance)
- cells resistant to MTX may not be resistant to PEMETREXED and other analogues (due to greater effects on thymidylate synthase rather than DHFR?)