Ion channel dysregulation in head and neck cancers: Perspectives for clinical application

Abstract

Head and neck cancers are a highly complex and heterogeneous group of malignancies that involve very diverse anatomical structures, and distinct aetiological factors, treatments and clinical outcomes. Among them, head and neck squamous cell carcinomas (HNSCC) are predominant, and the sixth most common cancer worldwide with still low survival rates. Omic technologies have unravelled the intricacies of tumour biology, harbouring a large diversity of genetic and molecular changes to drive the carcinogenesis process. Nonetheless, this remarkable heterogeneity of molecular alterations opens up an immense opportunity to discover novel biomarkers and develop molecular-targeted therapies. Increasing evidence demonstrates that dysregulation of ion channel expression and/or function is frequently and commonly observed in a variety of cancers from different origin. As a consequence, the concept of ion channels as potential membrane therapeutic targets and/or biomarkers for cancer diagnosis and prognosis has attracted growing attention. This chapter intends to comprehensively and critically review the current state-of-art on ion channel dysregulation specifically focusing on head and neck cancers, and to formulate the major challenges and research needs to translate this knowledge into clinical application. Based on current reported data, various voltage-gated potassium (Kv) channels (i.e. Kv3.4, Kv10.1 and Kv11.1) have been found frequently aberrantly expressed in HNSCC as well as precancerous lesions, and are highlighted as clinically and biologically relevant features in both early stages of tumourigenesis and late stages of disease progression. More importantly, they also emerge as promising candidates as cancer risk markers, tumour markers and potential anti-proliferative and anti-metastatic targets for therapeutic interventions; however, the oncogenic properties seem to be independent of their ion-conducting function.