The Unfolded Protein Response as a Therapeutic Target for Head and Neck Squamous Cell Carcinoma

Abstract

The epidemiology of head and neck malignancies and the survival rates for oral cancer patients are discussed in a cogent and thorough fashion throughout Targeting Oral Cancer. It is clear that a wide range of challenges, including disparity in health-care resources and research funding opportunities, and low prioritization by foundations and other organizations have left head and neck squamous cell carcinoma (HNSCC) patients in a remote corner of a huge outcome gap. Despite progress in multimodal therapies, responses to treatment and survival rates experienced by HNSCC patients lag egregiously behind the improvements that have been realized in other cancers. We should not lose focus of the fact that the 5-year survival rate for HNSCC is less than 50 % and very often accompanied by challenging and painful disfigurement. These dire statistics highlight the urgency of the problem. Also, comprehensive data indicating that ~70 % of HNSCC patients are still diagnosed at stages III or IV (Ferrari et al., Expert Opin Pharmacother 10(16):2625–32, 2009; Specenier and Vermorken, Expert Rev Anticancer Ther 8(3):375–91, 2008) underscores our need to diagnose patients sooner. Our continued inability to treat patients with chemotherapy whose metastatic and recurrent disease have outpaced the limitations of surgery and radiation therapy sentences them to an average median progression-free survival of ~6 months (Ferrari et al., Expert Opin Pharmacother 10(16):2625–32, 2009; Specenier and Vermorken, Expert Rev Anticancer Ther 8(3):375–91, 2008). Novel therapeutic targets and innovative strategies are urgently needed for a cancer that has seen little improvement over the last three decades. In this chapter we will discuss targeting the unfolded protein response (UPR) with small molecules and natural products as a novel anti-cancer approach in HNSCC models.