Review of STAT3 (Signal Transducers and Activators of Transcription) in head and neck cancer

Abstract

STATs can be activated independently of JAKs, most notably by c-Src kinases. In cancer cells, STAT3 and STAT5 activation leads to the increased expression of downstream target genes, leading to increased cell proliferation, cell survival, angiogenesis, and immune system evasion. STAT3 and STAT5 are expressed and activated in head and neck squamous cell carcinoma where they contribute to cell survival and proliferation. STATs can be activated by a number of signal transduction pathways, including the epidermal growth factor receptor (EGFR), nicotinic receptor, interleukin (IL) receptor, and erythropoietin receptor pathways. Identifying agents that inhibit STAT-3, a cytosolic transcription factor involved in the activation of various genes implicated in tumor progression is a promising strategy for cancer chemoprevention. Several approaches have been used to inhibit STAT3 in the hope of developing an antitumor agent. Although several STAT3-specific agents are promising, none are in clinical development, mostly because of drug delivery and stability issues.