Which transporter is involved in multidrug resistance (MDR)?
Multidrug resistance in oncology frequently originates from increased efflux reducing intracellular drug accumulation below cytotoxic threshold. ATP-binding cassette transporters, particularly ABCB1 P-glycoprotein, ABCC1 MRP1 and ABCG2 BCRP, are major contributors. They are primary active pumps using two ATP hydrolysis events per cycle to switch transmembrane domains from high-affinity inward-facing to low-affinity outward-facing state, literally vacuuming hydrophobic substrates from inner membrane leaflet. Their drug-binding pocket is large, flexible and polyspecific, accommodating anthracyclines, vinca alkaloids, taxanes, epipodophyllotoxins, tyrosine kinase inhibitors and immunosuppressants despite distinct structures. Physiologically these transporters localize at intestine, liver canaliculus, kidney tubule, blood-brain barrier and placenta providing xenobiotic protection. Overexpression after chemotherapy through gene amplification or transcriptional activation via pregnane X receptor leads to cross-resistance to many drugs, alters pharmacokinetics of orally administered compounds, and motivates development of third-generation inhibitors like tariquidar, though clinical success remains limited by toxicity and compensatory mechanisms. Such detailed mechanistic insight is frequently examined in competitive tests including NEET, CUET, CSIR-NET and GATE where transporter classification, energetics and disease linkage are integrated into problem-solving questions.
Ref: Gottesman et al., Nat Rev Cancer 2002, Multidrug resistance; Ambudkar et al., Annu Rev Pharmacol 1999.