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?
- A)Downregulation of VEGF in the tumor stroma
- B)Loss of topoisomerase II activity in tumor cells
- C)Overexpression of P glycoprotein encoded by MDR1GABARITO
- D)Inactivation of caspases by BCL2 loss
- E)Defective mismatch repair causing microsatellite instability only
Explicação
P glycoprotein, also called multidrug resistance protein 1, is an ATP dependent transmembrane efflux pump that exports many chemotherapeutic agents out of tumor cells. Its overexpression is a classic cause of acquired multidrug resistance after an initial trea... Ver explicação completa e trilha adaptativa →