Development of TGF-β signalling inhibitors for cancer therapy

Abstract
The transforming growth factor-β (TGF-β) superfamily of ligands has a pivotal role in the regulation of a wide variety of physiological processes from development to pathogenesis. Since the discovery of the prototypic member, TGF-β, almost 20 years ago, there have been tremendous advances in our understanding of the complex biology of this superfamily. Deregulation of TGF-β has been implicated in the pathogenesis of a variety of diseases, including cancer and fibrosis. Here we present the rationale for evaluating TGF-β signalling inhibitors as cancer therapeutics, the structures of small-molecule inhibitors that are in development and the targeted drug discovery model that is being applied to their development.