Resistance to cytotoxic drugs is thought to be a major cause of treatment failure in childhood
neuroblastoma, and members of the
ATP-binding cassette (
ABC) transporter superfamily may contribute to this phenomenon by active efflux of chemotherapeutic agents from
cancer cells. As a member of the C subfamily of
ABC transporters,
multidrug resistance-associated protein MRP4/ABCC4 has the ability to export a variety of endogenous and exogenous substances across the plasma membrane. In light of its capacity for chemotherapeutic drug efflux, MRP4 has been studied in the context of drug resistance in a number of
cancer cell types. However, MRP4 also influences
cancer cell biology independently of chemotherapeutic drug exposure, which highlights the potential importance of endogenous MRP4 substrates in
cancer biology. Furthermore, MRP4 is a direct transcriptional target of Myc family
oncoproteins and expression of this transporter is a powerful independent predictor of clinical outcome in
neuroblastoma. Together, these features suggest that inhibition of MRP4 may be an attractive therapeutic approach for
neuroblastoma and other
cancers that rely on MRP4. In this respect, existing options for MRP4 inhibition are relatively non-selective and thus development of more specific anti-MRP4 compounds should be a major focus of future work in this area.