Revisiting signal transducer and activator of transcription 3 (STAT3) as an anticancer target and its inhibitor discovery: Where are we and where should we go?

Abstract As a transcription factor, STAT3 protein transduces extracellular signals to the nucleus and then activates transcription of target genes. STAT3 has been well validated as an attractive anticancer target due to its important roles in cancer initiation and progression. Identification of specific and potent STAT3 inhibitors has attracted much attention, while there has been no STAT3 targeted drug approved for clinical application. In this review, we will briefly introduce STAT3 protein and review its role in multiple aspects of cancer, and systematically summarize the recent advances in discovery of STAT3 inhibitors, especially the ones discovered in the past five years. In the last part of the review, we will discuss the possible new strategies to overcome the difficulties of developing potent and specific STAT3 inhibitors and hope to shed light on future drug design and inhibitor optimization.