Abstract: Background: Oral cancer is a significant health concern worldwide, contributing to substantial morbidity and mortality. It predominantly affects regions such as Southeast Asia, with tobacco, alcohol use, and human papillomavirus (HPV) infection being major risk factors. Despite advancements in treatment modalities, including surgery, radiation therapy, and chemotherapy, survival rates for advanced oral cancer remain low. This has necessitated a shift in focus towards understanding the underlying molecular and metabolic pathways that drive oral cancer progression. Metabolic reprogramming, particularly alterations in glutamine metabolism, has gained attention as a hallmark of cancer, offering new avenues for therapeutic intervention.

Oral cancer, a major contributor to global cancer-related mortality, is characterized by aberrant metabolic alterations that sustain tumor growth, survival, and metastasis. Glutamine metabolism plays a pivotal role in the pathophysiology of oral cancer, providing critical intermediates for energy production, biosynthesis, and redox homeostasis. This paper explores the role of glutamine in oral cancer metabolism, examines the molecular mechanisms by which cancer cells hijack glutamine metabolism, and discusses potential therapeutic strategies targeting glutamine metabolism in the treatment of oral cancer.

Keywords: Oral Cancer, Glutamine Metabolism, Therapeutic Targets, Cancer Metabolism, Glutaminolysis, Redox Homeostasis, Tumor Growth, Metabolic Reprogramming, Glutamine Transporters, Glutaminase (GLS), MYC Oncogene, PI3K/AKT/mTOR Pathway, Hypoxia-Inducible Factor (HIF-1α), Oxidative Stress, Glutathione (GSH) Synthesis, Nucleotide and Lipid Biosynthesis, Cancer Cell Proliferation, Combination Therapies, Chemotherapy, Radiation Therapy, Immune Checkpoint Inhibitors, Tumor Microenvironment, Metabolic Interventions, α-Ketoglutarate (α-KG), Glucose Limitation

Abstract: Background: Oral cancer is a significant health concern worldwide, contributing to substantial morbidity and mortality. It predominantly affects regions such as Southeast Asia, with tobacco, alcohol use, and human papillomavirus (HPV) infection being major risk factors. Despite advancements in treatment modalities, including surgery, radiation therapy, and chemotherapy, survival rates for advanced oral cancer remain low. This has necessitated a shift in focus towards understanding the underlying molecular and metabolic pathways that drive oral cancer progression. Metabolic reprogramming, particularly alterations in glutamine metabolism, has gained attention as a hallmark of cancer, offering new avenues for therapeutic intervention.

Oral cancer, a major contributor to global cancer-related mortality, is characterized by aberrant metabolic alterations that sustain tumor growth, survival, and metastasis. Glutamine metabolism plays a pivotal role in the pathophysiology of oral cancer, providing critical intermediates for energy production, biosynthesis, and redox homeostasis. This paper explores the role of glutamine in oral cancer metabolism, examines the molecular mechanisms by which cancer cells hijack glutamine metabolism, and discusses potential therapeutic strategies targeting glutamine metabolism in the treatment of oral cancer.