Effects of a multi-targeted receptor tyrosine kinase inhibitor on radiosentization of head and neck squamous cell carcinoma. (127.21)

Abstract

Abstract Targeted biological therapies that selectively interfere with cancer cell growth signals may improve patient survival by enhancing the effects of radiation, with the added benefit of reduced systemic toxicity. Head and Neck Squamous Cell Carcinoma (HNSCC) is the most common epithelial malignancy arising in the upper aerodigestive tract. It is the sixth most common cancer worldwide. Signal transducers and activators of transcription 3 (STAT3), is present in a number of different cancer cells including head and neck cancer and is related to chemoresistance and radioresistance, therefore is a potential novel molecular target for therapy to improve survival of the patients. In the present study, we report that linifanib (ABT-869), is a novel multi-targeted receptor tyrosine kinase (RTK) inhibitor of members of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) receptor families, has anti-proliferative effects in HNSCC cell lines in a dose dependent manner. It inhibits STAT3 signaling and related proteins and arrests cell cycle at G2/M phase, induces apoptosis, inhibits colony formation efficiency of the cells. In addition, when this multi-targeted receptor tyrosine kinase inhibitor is combined with radiation, significant antitumor effects are achieved in the cell lines. Thus, it may provide a therapeutic strategy and improves efficacy of radiation against HNSCC.