(6) Decreased target: decreased topoisomerase I, e.g., etoposide 7 Gene amplification: Methotrexate (MTX)increase dihydrofolate reductase, hence requires more mtx to block (8) Decreased accumulation: Decreased uptake(Methotrexate --carrier protein decreases). Increased Efflux Multidrug Resistance, P-Glycoprotein(gP-170)in membrane, pumps drug out)• (6) Decreased target: decreased topoisomerase II, e.g., etoposide • (7) Gene amplification: Methotrexate (MTX) increase dihydrofolate reductase, hence Requires more MTX to block • (8) Decreased accumulation: Decreased uptake (Methotrexate -- carrier protein decreases). Increased Efflux (Multidrug Resistance, P-Glycoprotein (gP-170) in membrane, pumps drug out)