Deciphering the role of IL-1 signaling as an escape pathway in EGFR-dependent head & neck squamous cell carcinoma (HNSCC): implications for treatment.

Tumours stemming from the oral cavity, pharynx, larynx, salivary gland, and nasal cavity are collectively placed under Head and Neck Cancer. Overexpressed EGFR accounts for nearly 90% of Head and Neck Cancer. Cetuximab – a chimeric monoclonal antibody was designed to target the extracellular domain III of the EGFR to curtail tumour proliferation. Cetuximab + radiation is the standard therapy for metastatic Head and Neck Cancer, yet, relapse is marked by the aggressive progression of the disease and with a poor survival rate. Patient data acknowledge the role of IL-1 signaling in determining the overall survival in patients. Thus, it becomes imperative to establish the crucial role played by IL-1 cytokines in determining the overall tumorigenesis. In our study, the main intent is to decipher the role played by IL-1 signaling and to overhaul the current treatment strategies with the intention of improving their efficacy. We employed the FaDu tumour cell line and combinatorial drug action by employing both anti-EGFR and anti-IL-1/IL1R1 inhibitors concurrently and found to be more effective in the arrest of overall tumour proliferation compared to mono-therapy (anti-EGFR) alone. We ascertain that combinatorial drug action was found to be effective compared to monotherapy using classical anti-EGFR. Independently, we defined the efficacy of a laboratory-designed anti-IL-1 decoy receptor named human TRAP IL-1 in neutralizing the free IL-1 ligands and the aftermath effects in cells. The results demonstrated the neutralization of IL-1 by TRAP IL-1 besides EGFR boiled down the overall proliferative potential of tumour cells. Summarizing our finding, we verified that IL-1 signaling aids and abets in the proliferation of tumour cells alongside EGFR signaling, thus making both EGFR and IL-1/IL1R1 coupled targets and amending the current treatment strategy with the induction of anti-IL-1/IL1R1 on par with anti-EGFR might increase Progression-Free Survival and Overall Survival in patients.