TARGETING EGFR/ERK/FOS SIGNALING AS A NOVEL APPROACH FOR HPV-POSITIVE HEAD AND NECK CANCER TREATMENT

Squamous cell carcinoma of the head and neck (HNSCC) is the 6th most common cancer worldwide. It accounts for 600.000 new cases and 350.000 deaths every year. HNSCC can be subdivided into two distinct subgroups: HPV-positive and HPV-negative. They present very different features including etiological agent, age, socioeconomic status, prognosis, genetic landscape, and tissue differentiation. Nevertheless, all HNSCC patients are treated with the same therapies, comprising chemo- and radiotherapy, and/or surgery. Specific therapies for HPV-positive HNSCC are needed. HPV oncoproteins E6/E7 are the drivers of oncogenesis in HPV-related cancers and they can be used as targets for therapy. To this end, we studied the effects of the knock down of E6/E7 in HNSCC-positive cell lines and we looked for pharmacological treatments to downregulate E6/E7 levels. We found that targeting the EGFR/ERK/FOS signaling pathway induced a transcriptional reduction of E6/E7 and that the ERK inhibitor Ravoxertinib was effective in killing HPV-positive HNSCC cell lines. Thus, this is a potential novel approach to address HPV+ HNSCC cancer.