Glucose Deprivation of Tumor Cells via Selective Nutrient Delivery: A Potential Therapy for Metastatic Breast Cancer

BACKGROUND/AIM: Metastatic breast cancer remains a major clinical challenge despite the availability of various chemotherapeutic agents. Current metabolic inhibitors have limitations, prompting the need for innovative strategies that selectively target tumor cells while sparing normal tissues. This study aimed to propose a novel approach focused on depriving tumor cells of glucose while ensuring nutrient delivery to normal cells. MATERIALS AND METHODS: A comprehensive literature review was conducted using PubMed and Google Scholar. The proposed strategy involved focusing on studies that deplete glycogen stores in normal tissues through prolonged fasting, followed by administration of total parenteral nutrition (TPN) enriched with essential ingredients encapsulated in specialized liposomes. Three liposomal strategies were outlined: 1-pH-sensitive copolymer coating: liposomes coated with polyethylene glycol-poly-L-histidine (PEG-PLH) selectively release contents in normal tissues by binding glucose transporters (GLUTs) while avoiding tumor cell GLUTs. 2-Superhydrophobic fluorinated compounds: conjugation with trastuzumab targets HER2 ligands on tumor cells, preventing liposome accumulation in tumors. 3-Superhydrophobic Zwitterionic modifications: these create a hydration layer around liposomes, preventing passage through capillary walls and reducing tumor tissue accumulation. RESULTS: The strategies were designed to selectively reduce glucose availability to tumor cells while preserving normal cellular metabolism. The proposed liposomal modifications theoretically enhance targeted delivery and minimize off-target effects, providing a novel framework for metabolic therapy in metastatic breast cancer. CONCLUSION: , and clinical studies are warranted to validate its effectiveness and explore applicability to other solid tumors.