Practice question

Cancer multidrug efflux is dominated not by CFTR or P-type ATPases but by ABC transporters that expel amphipathic chemotherapeutics from cytoplasm. ABCB1 P-glycoprotein MDR1 is best studied, overexpressed in colonic, renal, adrenocortical carcinomas and after chemotherapy induction in leukemia, lymphoma and breast cancer. Its polyspecific hydrophobic binding chamber accommodates doxorubicin, daunorubicin, vinblastine, vincristine, paclitaxel and etoposide causing cross-resistance. ABCC1 MRP1 exports glutathione conjugates of drugs, ABCG2 BCRP expels mitoxantrone and topotecan. Expression correlates with poor response, reduced disease-free interval, and altered pharmacokinetics influencing oral bioavailability and blood-brain barrier penetration. Mechanistically transporter uses ATP hydrolysis at two NBDs to switch from inward-high affinity to outward-low affinity releasing drug. Inhibitors verapamil, cyclosporine, tariquidar attempted clinically to reverse resistance, but toxicity and redundant export pathways limit success, prompting development of nanoparticle formulations to bypass efflux and selective modulators. 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.