Using customized bioactive libraries and high throughput screening to identify new inhibitory drugs to manage head and neck squamous cell carcinomas

Abstract

Head and neck cancer is a public health problem in many parts of the world, and squamous cell carcinomas account for approximately 90% of these malignant tumors. Despite advances in treatment, head and neck squamous cell carcinoma (HNSCC) survival rates remain unsatisfactory and is mainly associated with advanced-stage diagnosis and drug resistance. Because of the severe morbidity and mortality of HNSCC, discovering new candidate drugs has been an urgent issue. Emerging evidence suggests that drug resistance is mediated by the presence of a highly adaptative subpopulation of cancer cells known as cancer stem cells (CSC). Previous results by our research group presented new therapies that target CSC from HNSCC. However, new approaches are needed yet due to radiotherapy toxicities and resistance against the current chemotherapy (Cisplatin), found mainly by CSC. Based on the current lack of a therapy options for HNSCC, we are proposing to evaluate a Food and Drug Administration (FDA)-approved Drug Library to identify new pharmacological agents capable of impacting the growth of HNSCC. Here, we will investigate 2,320 approved drugs in 2D and 3D culture models, by high-precision liquid handler and high-throughput assays. Proliferation, migration, and tumorspheres will be evaluated by functional assays. We expect to identify active molecules and define the target population that will most likely benefit from the therapy.