Metabolic signature of squamous cell carcinoma of the head and neck: Consequences of TP53 mutation and therapeutic perspectives. (August 2018)

• Record Type: Journal Article
• Authors: Wilkie, Mark D.; Lau, Andrew S.; Vlatkovic, Nikolina; Jones, Terence M.; Boyd, Mark T.
• Is Part Of: Oral oncology. Volume 83(2018)
• Page Start: 1
• Page End: 10
• Publication Date: 2018-08
• Subjects: Head and Neck Neoplasms/drug therapy -- Head and Neck Neoplasms/radiotherapy -- Head and Neck Neoplasms/genetics -- Head and Neck Neoplasms/metabolism -- Biomarkers, Tumor/metabolism -- Glycolysis/physiology -- Glycolysis/drug effects -- Glycolysis/radiation effects -- Reactive Oxygen Species/metabolism -- Tumor Suppressor Protein p53/genetics; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2018.05.018
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: Aerobic glycolysis constitutes the metabolic signature of SCCHN. TP53 mutation drives this glycolytic re-programming of metabolic circuitry. Anti-metabolic agents can be used to target this re-programming. This strategy preferentially targets typically aggressive TP53 mutant disease. Further pre-clinical in vivo work is required prior to clinical translation. 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.