INTRODUCTION: Signal transducer and activator of transcription 3 (STAT3) controls a key signaling pathway in the development of many malignant diseases. Several genetic studies have proven its central role in the regulation of apoptosis, proliferation, angiogenesis and immune responses making it an attractive target for cancer therapy.
AREAS COVERED: This article addresses the role of STAT3 in immune response modulation and highlights the contribution of STAT3 in inflammation-mediated tumorigenesis. We also review the rationale to use novel STAT3 inhibitors and list some of these inhibitors such as STA-21, IS3 295, S3I- M2001 and small molecule JAK2 inhibitors AZD1480 and AZ960 that have been found to be efficient against tumors. We summarize the efforts that have been made so far in identifying promising compounds and mention the barriers that need to be overcome for successful application of STAT3 inhibitors in clinics.
EXPERT OPINION: STAT3 is an important target in tumor biology based on its frequent activation in various tumors and its pleiotropic effects on different cell types. Screening large libraries of logically synthesized small molecule inhibitors is one way to rapidly generate many potential molecules, which can then be tested in different biologically relevant models. The stage is, therefore, set for the identification and development of novel STAT3 inhibitors that will, in the very near future, enter the clinical realm.
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