General Pathology USMLE Step 1 Practice Question
A 49-year-old woman with metastatic breast cancer (HR 98, BP 128/82, RR 16, T 37.2°C) initially responds to doxorubicin and cyclophosphamide but develops progression at 18 months. Current labs show elevated LDH at 520 U/L. Tumor rebiopsy demonstrates MDR1 gene overexpression with increased P-glycoprotein efflux pump activity, causing decreased intracellular drug accumulation. No hepatic metastases are present. Which resistance mechanism best explains her treatment failure?
Answer choices
- ADownregulation of VEGF in the tumor stroma
- BLoss of topoisomerase II activity in tumor cells
- COverexpression of P glycoprotein encoded by MDR1Correct answer
- DInactivation of caspases by BCL2 loss
- EDefective mismatch repair causing microsatellite instability only
- FIncreased expression of cytochrome P450 enzymes in hepatic microsomes
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