Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis

Abstract

Considering the great energy and biomass demand for cell survival, cancer cells exhibit unique metabolic signatures compared to normal cells. Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent neoplasms worldwide. Recent findings have shown that environmental challenges, as well as intrinsic metabolic manipulations, could modulate HNSCC experimentally and serve as clinic prognostic indicators, suggesting that a better understanding of dynamic metabolic changes during HNSCC development could be of great benefit for developing adjuvant anti-cancer schemes other than conventional therapies. However, the following questions are still poorly understood: (i) how does metabolic reprogramming occur during HNSCC development? (ii) how does the tumorous milieu contribute to HNSCC tumourigenesis? and (iii) at the molecular level, how do various metabolic cues interact with each other to control the oncogenicity and therapeutic sensitivity of HNSCC? In this review article, the regulatory roles of different metabolic pathways in HNSCC and its microenvironment in controlling the malignancy are therefore discussed in the hope of providing a systemic overview regarding what we knew and how cancer metabolism could be translated for the development of anti-cancer therapeutic reagents.

Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis

“…Previous studies have sought to target different cancer-specific metabolic pathways, in particular glycolysis, for development of antitumor treatments (6)(7)(8)(9). There are three irreversible reactions in glycolysis.…”

Prognostic Value of the Overexpression of Fatty Acid Metabolism-Related Enzymes in Squamous Cell Carcinoma of the Head and Neck

“…Previous studies on cellular metabolism in SCCHN have revealed dysregulation in multiple metabolic pathways in tumors, such as the mitochondrial oxidative phosphorylation and the tricarboxylic acid cycle [ 10 ], and in the utilization of glucose as a dominant energy source for the survival and proliferation of SCCHN cells [ 11 ]. Despite the endeavors in targeting aerobic glycolysis in the treatment of SCCHN, no glycolytic inhibitors have been used in the clinical setting so far [ 12 ], suggesting that SCCHN cells might have alternative metabolic pathways to acquire energy to survive. Our previous study, and a study by another group, have shown that overexpression of phosphorylated inhibitory ACC1 or ACC2 was associated with a decreased survival rate in SCCHN [ 4 , 5 ].…”

Nuclear Magnetic Resonance Metabolomics Biomarkers for Identifying High Risk Patients with Extranodal Extension in Oral Squamous Cell Carcinoma

“…Cancer cells have been reported to have altered metabolism in glycolysis, which is called the "Warburg effect", and several other metabolic pathways are yet to be elucidated. Accumulated evidence has shown that the host-environmental manipulations could modulate the metabolism in OSCC and potentially serve as clinic prognostic indicators or developing adjuvant anti-cancer therapy [12]. Metabolomics may be a comprehensive approach to clarify the entire metabolic system that plays a role in OSCC.…”