Metabolic signature of squamous cell carcinoma of the head and neck: Consequences of TP53 mutation and therapeutic perspectives

Abstract

There is a pressing need to identify ways of sensitising squamous cell carcinomas of the head and neck (SCCHN) to the effects of current treatments, both from oncological and functional perspectives. Alteration to cellular metabolism is now widely considered a hallmark of the cancer phenotype; presents a potentially attractive therapeutic target in this regard; and as such has received renewed research interest in recent years. However, whilst metabolic disruption may occur to some degree in all tumours, there is undoubtedly heterogeneity and detailed study of individual tumour types is paramount if effective therapeutic strategies targeting metabolism are to be developed and effectively deployed. In this review we outline current understanding of altered tumour metabolism and how these adaptations promote tumorigenesis generally. We relate this specifically to SCCHN by focusing on several recent key studies specific to SCCHN, and by discussing the role TP53 mutation may play in this metabolic switch, given the fundamental role of this oncogenic event in SCCHN tumorigenesis. Finally, we also offer insight into the potential therapeutic implications this may have in the clinical setting and make recommendations for future study.

Keywords: Biomarkers, Tumor/metabolism; Glycolysis/drug effects; Glycolysis/physiology; Glycolysis/radiation effects; Head and Neck Neoplasms/drug therapy; Head and Neck Neoplasms/genetics; Head and Neck Neoplasms/metabolism; Head and Neck Neoplasms/radiotherapy; Reactive Oxygen Species/metabolism; Tumor Suppressor Protein p53/genetics.