Hypoxia-Driven Alterations in the Tumour Microenvironment of Oral Cancer

Tumour hypoxia significantly influences disease advancement and treatment resistance in oral squamous cell carcinoma (OSCC). Hypoxia-inducible factor-1α (HIF-1α) is preserved when oxygen is lacking and triggers the expression of hypoxia-responsive genes that have roles in angiogenesis, metabolic adaptability, tumour cell viability, invasion, and metastasis. The elevated levels of vascular endothelial growth factor (VEGF) induced by HIF-1α result in atypical angiogenesis. The dysfunction of cell junction proteins and heightened activity of matrix metalloproteinases caused by hypoxia facilitate cancer invasion and metastasis. Hypoxic stress prompts cellular modifications, including autophagy and the preservation of cancer cell populations with enhanced survival capabilities, hence facilitating tumour recurrence and heterogeneity. Hypoxia diminishes the effectiveness of standard chemotherapy and radiotherapy due to decreased drug transport, hindered cell growth, and diminished oxygen-dependent radiation-induced DNA damage. Thus, treatment strategies for the hypoxic tumour microenvironment encompass the suppression of HIF and VEGF, tumour reoxygenation, hypoxia radiosensitizers, and hypoxia-activated lethal compounds. Nonetheless, the diverse and fluctuating characteristics of tumour hypoxia, along with the initiation of compensatory survival mechanisms, continue to pose significant obstacles. Enhanced comprehension of hypoxia-induced molecular networks and the advancement of multimodal, biomarker-directed treatment strategies could improve outcomes in OSCC.