Metabolic reprogramming in head and neck cancer: therapeutic opportunities and challenges

This review explores the metabolic pathways involved in the survival and apoptosis of head and neck cancer (HNC) cells, with a focus on how altered metabolism supports tumour growth and resistance to therapy.

Relevant literature was retrieved from Scopus using the keywords: 'head and neck squamous cell carcinoma', 'glycolysis', 'the Warburg effect', and 'metabolism'. Articles published in English were included without time restrictions.

Head and neck cancers (HNCs) exhibit dynamic and adaptable metabolic activity that supports proliferation and survival. Cancer cells often reprogramme their metabolism based on cell type, genetic alterations, and environmental conditions. A prominent feature is their reliance on glucose, demonstrated by elevated glucose uptake and increased glycolysis even under normoxic conditions-a phenomenon known as 'the Warburg effect'. However, nutrient limitation may paradoxically promote tumour aggressiveness. Beyond glycolysis, evidence shows that HNC cells can exploit alternative metabolic pathways, such as lipid and amino acid metabolism, particularly when glucose becomes scarce. These metabolic adaptations present potential pharmaceutical targets for therapeutic intervention.

HNCs rely on flexible metabolic pathways to support growth and resist treatment. Their dependence on glucose and ability to shift to lipid and amino acid metabolism offer promising targets for therapy.