STAT3 as a central mediator of neoplastic cellular transformation

Much of the focus in understanding the molecular pathogenesis of tumors has centered on kinases that are activated in cancer. However, cancers driven by a diversity of activated kinases may have very similar pathological and clinical properties. This likely relates to the fact that the biological characteristics of a tumor are driven by the pattern of gene expression in that tumor, and that a wide spectrum of activating events at the cell surface and in the cytoplasm converge on a relatively small number of transcription factors that regulate the expression of key target genes. One transcription factor that has been found to be activated inappropriately in a wide range of human cancers is STAT3. STAT3 target genes are involved in fundamental events of tumor development including proliferation, survival, self-renewal, invasion, and angiogenesis. Furthermore, there is strong evidence that STAT3 is critical for these processes, in that inhibition of STAT3 by a variety of means can exert an anti-cancer effect. Since normal cells are relatively tolerant of interruption in STAT3 signaling, these findings suggest that STAT3 may also be an excellent target for the molecular therapy of cancer.