Urokinase Receptor (uPAR) Ligand based Recombinant Toxins for Human Cancer Therapy

The urokinase receptor (uPAR) exerts essential functions in the pathophysiology of cancers and therefore constitutes an important drug target. In order to generate efficient drugs against uPAR, a new approach includes chimeric proteins associating one molecular address to specifically target uPAR and one bacterial or plant toxin that will eventually kill the tumoral cell. Using this frame, several recombinant toxins have been designed namely DTAT, DTAT13, EGFATFKDEL 7 mut, and ATF-SAP. As molecular address, all of these fusion proteins use the amino-terminal fragment of urokinase that binds with high affinity to uPAR through its growth factor domain (GFD). The various toxin moieties were derived from either diphtheria toxin, Pseudomonas exotoxin A (PE38), or saporin. In this review, we describe the rational, design, production and therapeutic anti-cancer potential of these chimeric toxins.