Investigation of potential use of FGFR inhibitor AZD4547 against taxol resistance in head and neck cancer cells using in vitro tests

Head and neck cancers are among the most frequent cancers worldwide. Although taxol is widely used for the treatment of many cancer types, including head and neck cancers, resistance to taxol negatively affects the treatment processes. To the best of our knowledge, there is no study reporting any resistance mechanism developed against taxol in head and neck cancers occurring through the activation of FGFR2/AKT/SOX2 axis. In this thesis study, we aimed at investigating the effects of AZD4547 alone or in combination with taxol on cancer associated phenotypes and to examine the potential of AZD4547 to overcome resistance developed against taxol in head and neck cancer cells. Inıtially, the potential of AZD4547 to inhibit FGFR2 and its downstream targets in head and neck cancer cells and the status of FGFR2/AKT/SOX2 axis in tumor/normal tissue pairs were analyzed by western blot. Then, the effects of AZD4547 and taxol in head and neck cancer cells and AZD4547 in taxol resistant Hep-2 cells on the cell viability, cell migration and colony forming potential were investigated. We showed that FGFR2 and its downstream targets were highly expressed in tumor tissues than corresponding normal tissues, and AZD4547 effectively inhibited FGFR2 and its downstream targets. In addition, we demonstrated that AZD4547 reduces cell viability, cell migration and colony formation potential, and its co-treatment with taxol increases the impact of taxol on cancer cells. We also found that AZD4547 inhibits the overexpressed FGFR2/ AKT/SOX2 axis and effectively suppresses cancer-related cellular phenotypes in Hep-2 cells that are resistant to taxol. Our results revealed preliminary data that AZD4547 could increase the effects of taxol in the treatment process in head and neck cancer, and we suggest AZD4547 as a therapeutic alternative to overcome the resistance to taxol.