Targeting the TGFβ signalling pathway in disease

The transforming growth factor-β (TGFβ) signalling pathway is implicated in a variety of disorders, including cancer, fibrosis and inflammation, and has become an attractive target for drug development. Here, Akhurst and Hata present therapeutic strategies for intervening in this pathway and discuss agents currently under investigation while addressing the associated challenges in their development and application. Many drugs that target transforming growth factor-β (TGFβ) signalling have been developed, some of which have reached Phase III clinical trials for a number of disease applications. Preclinical and clinical studies indicate the utility of these agents in fibrosis and oncology, particularly in augmentation of existing cancer therapies, such as radiation and chemotherapy, as well as in tumour vaccines. There are also reports of specialized applications, such as the reduction of vascular symptoms of Marfan syndrome. Here, we consider why the TGFβ signalling pathway is a drug target, the potential clinical applications of TGFβ inhibition, the issues arising with anti-TGFβ therapy and how these might be tackled using personalized approaches to dosing, monitoring of biomarkers as well as brief and/or localized drug-dosing regimens.