Glucose metabolic reprogramming: a novel strategy to enhance radiotherapy response to triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by poor prognosis and limited responsiveness to conventional therapies. Increasing evidence shows that the reprogramming of glucose metabolism is a hallmark of cancer cells, supporting their rapid proliferation, metastatic potential, and therapy resistance. This metabolic shift is particularly pronounced in TNBC, where reliance on glycolysis is greater than in other breast cancer subtypes. Consequently, strategies that target glucose metabolic pathways may offer a promising means to overcome treatment resistance and improve clinical outcomes. In this review, we summarize the unique features and regulatory mechanisms of glycolytic reprogramming in TNBC, with attention to tumor heterogeneity and its implications for disease progression and treatment response. We highlight recent preclinical studies that evaluate therapeutic approaches designed to exploit metabolic vulnerabilities, including glycolysis inhibition, metabolic enzyme targeting, and combination regimens with radiotherapy. Collectively, these findings suggest that interventions aimed at glycolytic pathways hold considerable potential to enhance radiosensitivity in TNBC. We discuss the translational prospects of this research, emphasizing the value of glycolysis-related genes as predictive biomarkers and as foundations for the development of novel targeted agents. While preliminary evidence is encouraging, further validation is required to establish the safety, efficacy, and clinical applicability of these strategies in human patients. Continued research in this area is expected to contribute to the development of more effective therapeutic options, ultimately improving the management and prognosis of TNBC.