Inhibiting receptor tyrosine kinases has been a cornerstone of cancer therapeutics for decades. Treatment strategies largely involve small-molecule kinase inhibitors and monoclonal antibodies. For receptors activated by constitutively dimeric ligands, another potential mechanism of inhibition exists: developing monomeric ligands that prevent receptor dimerization. In a recent issue of the Biochemical Journal, Zur et al. [Biochem. J. (2017) 474, 2601-2617] describe the details of creating such an inhibitor directed toward the macrophage colony-stimulating factor receptor, c-FMS. In the process of teasing apart the ligand dimer, they also uncover a potential cryptic regulatory mechanism in this receptor subfamily.
Keywords: inhibition; receptor tyrosine kinases; signaling.
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.