FIBROBLAST GROWTH FACTOR RECEPTORS IN HEAD AND NECK CANCER: TRANSLATIONAL STUDIES ON PROGNOSIS AND THERAPY

Abstract

Objective Fibroblast growth factor receptors (FGFR1–4) are promising therapeutic targets in multiple types of solid tumors. However, for head and neck squamous cell carcinoma (HNSCC) evidence on FGFR is limited. We have investigated the therapeutic and prognostic value of all four FGFR family members in head and neck squamous cell carcinoma. Novel therapeutic targets and prognostic markers are highly demanded since patient survival remains poor and treatment options are often limited. Methods Molecular techniques to determine the therapeutic and prognostic value included immunohistochemistry, FISH and DNA sequencing on HNSCC tissues, and FGFR-inhibitor experiments on HNSCC cell lines. Molecular findings were related to clinical patient and pathologic tumor characteristics. Results FGFR1-4 proteins were frequently overexpressed in HNSCC tissues (39–79%) and high FGFR1 expression was related to poor overall and disease-free survival in HPV-negative HNSCC (HR: 3.07 CI: 1.74–6.90 p = 0.001 and HR: 1.53 CI: 1.04–2.39 p = 0.033).The FGFR genes were aberrated in a minor subset of HNSCC (3%). Treatment of the high FGFR1-expressing cell line CCL30 with AZD4547 reduced cell proliferation and FGFR signaling. Combined AZD4547 and gefitinib treatment synergistically inhibited the proliferation of resistant cell lines SCC147 and BICR16. Conclusion Here, we identify FGFR family members as novel potential therapeutic targets for FGFR-inhibitor therapy in head and neck squamous cell carcinoma. In addition, we identify FGFR1 as a candidate prognostic biomarker in HPV-negative HNSCC. We provide a rationale for targeting FGFR in HNSCC patients.