Expression of multidrug transporter MRP4/ABCC4 is a marker of poor prognosis in neuroblastoma and confers resistance to irinotecan in vitro

摘要: Members of the multidrug resistance-associated protein (MRP) family transporters are believed to contribute cytotoxic drug resistance and chemotherapy failure. We observed frequent MRP4 overexpression in aggressive primary neuroblastoma, a disease for which we have previously shown MRP1 be prognostic indicator. High expression correlated with MYCN oncogene amplification was significantly associated poor clinical outcome. Although is known transport some nucleoside analogues, it has not been drugs used treat solid tumors. now show that mediates substantial vitro topoisomerase I poison irinotecan/CPT-11 its active metabolite SN-38. These results suggest will useful marker neuroblastoma trials irinotecan as treatment should monitor expression. The same may true other tumor types expressing high levels transporter.