FGF expression in HPV16-positive and -negative SCC after treatment with small-molecule tyrosine kinase inhibitors and everolimus

• Verfasst von: Huber, Lena [VerfasserIn]
• Verfasst von: Birk, Richard [VerfasserIn]
• Verfasst von: Knüttel, Manuel Thomas [VerfasserIn]
• Verfasst von: Rotter, Nicole [VerfasserIn]
• Verfasst von: Aderhold, Marc Christoph [VerfasserIn]
• Verfasst von: Scherl, Claudia [VerfasserIn]
• Verfasst von: Lammert, Anne [VerfasserIn]
• Verfasst von: Jungbauer, Frederic [VerfasserIn]
• Verfasst von: Kramer, Benedikt [VerfasserIn]
• Titel: FGF expression in HPV16-positive and -negative SCC after treatment with small-molecule tyrosine kinase inhibitors and everolimus
• Verf.angabe: Lena Huber, Richard Birk, Manuel Knuettel, Nicole Rotter, Christoph Aderhold, Claudia Scherl, Anne Lammert, Frederic Jungbauer and Benedikt Kramer
• E-Jahr: 2020
• Jahr: October 2020
• Umfang: 10 S.
• Illustrationen: Illustrationen
• Fussnoten: Online publiziert: 28. September 2020 ; Gesehen am 21.07.2025
• Titel Quelle: Enthalten in: Anticancer research
• Ort Quelle: Kapandriti, Attiki, Greece : International Institute of Anticancer Research, 2004
• Jahr Quelle: 2020
• Band/Heft Quelle: 40(2020), 10 vom: Okt., Seite 5621-5630
• ISSN Quelle: 1791-7530
• DOI: doi:10.21873/anticanres.14575
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: everolimus
• Sach-SW: FGF
• Sach-SW: Fibroblast growth factor
• Sach-SW: head and neck squamous cell carcinoma
• Sach-SW: HNSCC
• Sach-SW: HPV
• Sach-SW: mTOR inhibitors
• Sach-SW: tyrosine kinase inhibitors
• K10plus-PPN: 1931395195

Abstract

Background: Targeted therapies in the treatment of head and neck squamous cell carcinoma (HNSCC) are subject to extensive research. Different mutations of genes belonging to the fibroblast growth factor (FGF) family have been detected in HNSCC. In this study, we examined the expression of FGF1 and FGF2 after treatment with small-molecule tyrosine kinase inhibitors (TKIs) and an inhibitor of mechanistic target of rapamycin (mTOR) in vitro using human papillomavirus (HPV)-positive and -negative SCC lines. Materials and Methods: Cells of two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with 20 μmol/l of erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay and the protein concentrations of FGF1 and FGF2 by sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those for untreated HPV-negative SCC cells. Results: FGF1 and FGF2 were detected in all three tested cell lines. The tested TKIs significantly (p<0.05 reduced) FGF1 expression in the UMSCC-11A cell line within the first 24 h. At later time points, the tested TKIs and everolimus significantly (p<0.05) increased FGF1 and FGF2 expression in HPV-negative and -positive cancer cell lines. The effect was stronger in the HPV-positive cell line. Conclusion: Alterations in FGF signalling are considered to be relevant drivers of tumourigenesis in some HNSCCs. Our results show that the expression of FGF1 and -2 can be influenced effectively by small-molecule TKIs and everolimus. Based on our data, future research should include combinations of specific FGF inhibitors, mTOR inhibitors and other TKIs in the treatment of HNSCC and research on FGF-mediated drug escape mechanisms.