Interleukin-6 as a therapy target in oral squamous carcinoma

Introduction: Interleukin-6 (IL-6) is a multifunctional cytokine which is implicated in the regulation of immune responses and cellular events. It may activate signaling pathways of Janus kinase/signal transducer and activator of transcription (JAK/STAT) factors, mitogen-activated protein kinases, and Akt. IL-6 could exert pleiotropic effects in a variety of cancers. Areas covered: Oral squamous cell carcinoma epidemiology, pathology, regulation by IL-6, and experimental therapy. Expert opinion: Oral squamous cell carcinoma development is in part facilitated by chronic epithelial irritations and this tumor is more frequent in smokers or individuals who consume excessive amounts of alcohol. IL-6 levels are elevated in this neoplasm and IL-6 is considered a bad prognostic factor in oral cancer. IL-6 secretion in oral squamous cancer is facilitated by the microenvironment, in particular by stromal derived factor-1. IL-6 function in non-malignant and malignant diseases is controlled by endogenous inhibitors of cytokine signaling. IL-6 action in oral squamous cancer is largely mediated by the JAK/STAT3 pathway and may lead to epithelial to mesenchymal transition, thus contributing to tumor progression. IL-6 also enhances angiogenesis and lymphangiogenesis through regulation of vascular endothelial growth factor. In addition, experimental anti-IL-6/anti-IL-6 receptor-targeted therapies in oral cancer have been proposed.