Na+/K+-ATPase α subunits as new targets in anticancer therapy

Background: The sodium pump (Na+/K+-ATPase) could be a target for the development of anticancer drugs as it serves as a signal transducer, it is a player in cell adhesion and its aberrant expression and activity are implicated in the development and progression of different cancers. Cardiotonic steroids (CS) are the natural ligands and inhibitors of the sodium pump and this supports the possibility of their development as anticancer agents targeting overexpressed Na+/K+-ATPase alpha subunits. Objectives: To highlight and further develop the concept of using Na+/K+-ATPase alpha 1 and alpha 3 subunits as targets in anticancer therapy and to address the question of the actual usefulness of further developing CS as anticancer agents. Conclusions: Targeting overexpressed Na+/K+-ATPase a subunits using novel CS might open a new era in anticancer therapy and bring the concept of personalized medicine from aspiration to reality. Clinical data are now needed to further support this proposal. Furthermore, future medicinal chemistry should optimize new anticancer CS to target Na+/K+-ATPase alpha subunits with the aim of rendering them more potent and less toxic.