Overcoming Resistance to Standard-of-Care Therapies for Head and Neck Squamous Cell Carcinomas.

Although there have been some advances during in recent decades, the treatment of head and neck squamous cell carcinoma (HNSCC) remains challenging. Resistance is a major issue for various treatments that are used, including both the conventional standards of care (radiotherapy and platinum-based chemotherapy) and the newer EGFR and checkpoint inhibitors. In fact, all the non-surgical treatments currently used for HNSCC are associated with intrinsic and/or acquired resistance. Herein, we explore the cellular mechanisms of resistance reported in HNSCC, including those related to epigenetic factors, DNA repair defects, and several signaling pathways. This article discusses these mechanisms and possible approaches that can be used to target different pathways to sensitize HNSCC to the existing treatments, obtain better responses to new agents, and ultimately improve the patient outcomes.

HTS Identification of Activators and Inhibitors of Endoplasmic Reticulum (ER) Stress and the Unfolded Protein Response (UPR).

The identification of small molecules and natural product extracts that enhance or interfere with the productivity of protein folding in the endoplasmic reticulum (ER) has the potential to improve a wide variety of human pathologies. Every protein that is destined for a lysosome, integral to the cell membrane, or secreted, is folded, post-translationally modified, and exported to the cytoplasm from the ER-Golgi complex. The following protocols have successfully employed several high-fidelity cell-based luciferase high-throughput screens (HTS) to identify activators and inhibitors of ER stress and the unfolded protein response (UPR).