Therapeutic modulators of STAT signalling for human diseases

Members of the signal transducer and activator of transcription (STAT) protein family are implicated in a variety of diseases. In particular, aberrant activation of STAT3 is known to promote malignant transformation. In this Review, Turkson and colleagues discuss the various therapeutic approaches used to modulate the activation of the different STAT family members, which include dimerization inhibitors, tyrosine kinase inhibitors and DNA decoys. The signal transducer and activator of transcription (STAT) proteins have important roles in biological processes. The abnormal activation of STAT signalling pathways is also implicated in many human diseases, including cancer, autoimmune diseases, rheumatoid arthritis, asthma and diabetes. Over a decade has passed since the first inhibitor of a STAT protein was reported and efforts to discover modulators of STAT signalling as therapeutics continue. This Review discusses the outcomes of the ongoing drug discovery research endeavours against STAT proteins, provides perspectives on new directions for accelerating the discovery of drug candidates, and highlights the noteworthy candidate therapeutics that have progressed to clinical trials.