STAT signaling in head and neck cancer

The upper aerodigestive tract is predisposed to the formation of multiple p rimary tumors due to field cancerization. TGF-alpha/EGFR autocrine signalin g appears to play an important role in squamous cell carcinoma of the head and neck (SCCHN) and upregulation of TGF-alpha and EGFR is an early event i n SCCHN carcinogenesis. STAT proteins, including Stat3, are activated by TG F-alpha and EGFR and strategies that downmodulate TGF-alpha or EGFR inhibit SCCHN cell proliferation and abrogate Stat3 activation. Targeting Stat3 le ads to SCCHN growth inhibition, increases apoptosis and a downmodulation of Bcl-x(L) expression in head and neck tumors. These studies support the rol e of Stat3 as an oncogene, which is activated early in SCCHN carcinogenesis , and efforts to understand EGFR-mediated Stat3 signaling could facilitate novel strategies that will interfere with this growth promoting pathway.