Inflammatory cytokine signaling contributes to Erlotinib resistance in head and neck squamous cell carcinoma

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) is a major obstacle in the success of head and neck cancer therapy. Despite efforts by several groups to understand the mechanisms of resistance to tyrosine kinase inhibitors such as erlotinib, there has been little success in improving the patient survival. Given that there are a number of ongoing clinical trials testing the efficacy of erlotinib in head and neck cancer, it is essential to investigate the novel mechanisms of erlotinib resistance to improve its efficacy and patient survival. This dissertation addresses this issue of erlotinib resistance in head and neck cancer, underscoring the role of inflammatory cytokine signaling. Chapter 1 introduces the problem of erlotinib resistance and discusses the potential link between inflammatory signaling and cancer progression and erlotinib resistance in head and neck squamous cell carcinoma. Chapter 2 discusses the role of the cytokine interleukin-6 signaling in acquired resistance to erlotinib in head and neck squamous cell carcinoma. Chapter 3 describes the role of IL-1 signaling in acquired resistance to erlotinib in head and neck squamous cell carcinoma. Chapter 4 discusses the specific role of IL-1α (an agonistic ligand for IL-1 signaling) in acquired resistance to erlotinib in head and neck squamous cell carcinoma. Chapter 5 discusses ideas to test for future work in this field. Altogether, this dissertation endeavors to emphasize the contributory role of inflammatory cytokine signaling in erlotinib resistance in head and neck squamous cell carcinoma so that it helps in the development of effective anti-cancer therapies and biomarkers of resistance and/or response in HNSCC.