315 (PB095) - Cisplatin resistance of TMEM16A overexpressing head and neck tumors and cancer models is driven by increased lysosomal flux and reversed by Hydroxychloroquine

Abstract

Background. Squamous cell carcinoma of the head and neck (SCCHN) is the sixth deadliest tumor worldwide. Despite the advances in therapies, this disease has low cure rates. Approximately 30% of SCCHN tumors amplify chromosomal band 11q13, which harbors the ANO1 gene that encodes the calcium-activated chloride ion channel TMEM16A. TMEM16A overexpression in SCCHN is associated with poor response to cisplatin and reduced survival. The mechanisms of cisplatin resistance in TMEM16A-overexpressing tumors are unclear; finding them would suggest new combinatorial therapy targets for SCCHN.