ABCG2 Transporter Expression Impacts Group 3 Medulloblastoma Response to Chemotherapy

摘要: While a small number of plasma membrane ABC transporters can export chemotherapeutic drugs and confer drug resistance, it is unknown if these are expressed or functional in less therapeutically tractable cancers such as Group3 medulloblastoma (G3 MB). Herein we show that among this class only ABCG2 was at highly increased levels human G3 MB mouse model disease. In the model, Abcg2 protein where functioned expected based on prototypical substrates. By screening substrates against tumorspheres vitro, found inhibition could potentiate responses to clinically employed topotecan, producing >9-fold suppression cell proliferation. Extended studies vivo confirmed sufficient enhance antiproliferative significant survival advantage compared subjects treated with topotecan alone. Our findings offer preclinical proof concept for blockade transporter activity strategy empower medulloblastoma.