ANTI-ANGIOGENIC TARGETED THERAPY FOR FELINE ORAL SQUAMOUS CELL CARCINOMA: TOWARDS A NEW ERA OF VETERINARY ONCOLOGY

Current therapeutic approaches (surgery, chemo- and radiotherapy) for feline oral squamous cell carcinoma (FOSCC) are not efficient, so the prognosis is often poor [1]. FOSCC is a reliable animal model of human head and neck SCC (HNSCC), with which it shares biological and molecular aspects, such as expression of the pro-angiogenic molecule known as vascular endothelial growth factor (VEGF) [1]. Angiogenesis is a main feature of many types of cancer, including HNSCC, where it plays a key role in tumor growth and metastasis [2]. Numerous studies and clinical trials testing anti-angiogenic drugs against HNSCC have shown encouraging results, with the anti-VEGF monoclonal antibody (mAb) Bevacizumab appearing as the most promising one [2]. Bevacizumab binds to VEGF and inhibits activation of its main receptor, the VEGFR-2, resulting in anti-tumor effects [2]. Interestingly, human and feline VEGF display high sequence homology, and Bevacizumab has been shown to bind also to feline VEGF [3]. Based on this background, the objective of this work was to preliminarily assess the possible transferability of anti-angiogenic targeted therapy in FOSCC in vitro models. Firstly, expression of VEGF and VEGFR-2 were assessed in three FOSCC-derived cell lines by biochemical and molecular biology techniques, such as Western blotting (WB) and Reverse Transcription-PCR (RT-PCR). Once their expression was assessed, the effects of treatment with Bevacizumab on VEGFR-2 activation was investigated. To this aim, one human cell line (as control) and two FOSCC cell lines were treated with this mAb at different doses (25, 50,100 μg/mL) and collected at different time points (0, 1h, 3h, 6h) to be analyzed by WB for expression and phosphorylation of VEGFR-2 and its downstream molecules such as ERK and Akt. Results showed that Bevacizumab impairs activation of VEGFR-2, ERK and Akt in all the analyzed FOSCC cell lines. The long-term objective of this research is to put the rationale for future clinical trials in the feline host to confirm the efficacy of anti-angiogenic targeted therapy against FOSCC, in order to add mAbs as new weapons into the anti-cancer arsenal in veterinary medicine