Inhibition of fibroblast growth factor receptor with AZD4547 mitigates juvenile nasopharyngeal angiofibroma

• DOI: 10.1002/alr.21987
• Publication Date: 2017-07-14T10:46:35Z
• Authors: Tran Le; Jacob New; Joel W. Jones; Shireen Usman; Sreeya Yalamanchali; Ossama Tawfik; Larry Hoover; Dan E. Bruegger; Sufi Mary Thomas
• Keywords: Juvenile nasopharyngeal angiofibroma

Background Juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor that presents in adolescent males. Although surgical excision the mainstay of treatment, recurrences complicate treatment. There need to develop less invasive approaches for management. JNA tumors are composed fibroblasts and vascular endothelial cells. We identified fibroblast growth factor receptor (FGFR) (VEGF) expression JNA‐derived fibroblasts. FGFR influences proliferation VEGF necessary angiogenesis. hypothesized targeting would mitigate proliferation, invasion, migration, attenuate tubule formation. Methods After informed consent, from explants 3 patients were isolated. Fibroblasts treated with inhibitor AZD4547, 0 25 μg/mL 72 hours was quantified using CyQuant assay. Migration invasion assessed 24‐hour transwell assays subsequent fixation quantification. Mitigation downstream signaling evaluated by immunoblotting. Tubule formation human umbilical vein cells (HUVECs) vehicle control (dimethylsulfoxide [DMSO]) or semaxanib (SU5416) as well serum‐free media (SFM) conditioned (CM). length compared between treatment groups. Results Compared control, AZD4547 inhibited through inhibition signaling, specifically phosphorylation ‐ p44/42 mitogen activated protein kinase (p44/42 MAPK). CM significantly increased HUVEC ( p = 0.0039). Conclusion effectively mitigates decreases invasion. SU5416 attenuated fibroblast‐induced may have therapeutic potential JNA.