Metabolism and Metabolic Reprogramming in Laryngeal Squamous Cell Carcinoma

Laryngeal squamous cell carcinoma (LSCC) remains a major clinical challenge within head and neck oncology, with five-year survival rates showing minimal improvement over recent decades despite advances in surgical and multimodal therapeutic strategies. Increasing evidence identifies metabolic reprogramming as a central driver of tumor progression, therapeutic resistance, and immune evasion in LSCC. Beyond the classical Warburg effect, LSCC exhibits profound metabolic reprogramming, involving coordinated alterations in carbohydrate, amino acid, lipid, and iron metabolism that support adaptation to hypoxic and nutrient-deprived microenvironments. Hypoxia-inducible factors, particularly HIF-1 alpha, coordinate these key biochemical pathways and enzymatic steps by integrating glycolysis, glutaminolysis, folate-dependent one-carbon pathways, lipid synthesis, and mitochondrial remodeling, while also influencing stromal and immune components of the tumor microenvironment. Metabolic crosstalk between tumor cells, cancer-associated fibroblasts, and immune populations promotes immunosuppression through nutrient competition and accumulation of metabolites such as lactate and lipid-derived mediators. In parallel, dysregulated iron handling and altered ferroptosis susceptibility emerge as key determinants of tumor aggressiveness and treatment response. This review synthesizes current evidence on metabolic rewiring in laryngeal squamous cell carcinoma, highlighting how alterations in metabolic pathways create targetable vulnerabilities that drive tumor biology, immune modulation, and resistance to conventional and emerging therapies. Elucidating these metabolic dependencies may support the development of metabolism-based biomarkers and therapeutic strategies in laryngeal squamous cell carcinoma, providing an integrated and translational perspective that links tumor metabolism with microenvironmental interactions and immune modulation, while highlights emerging therapeutic vulnerabilities.