Impact of Slow- Infusion (Metronomic) 2-Deoxy-D-Glucose in Treatment of Refractory Patient of Gliobalstoma Multiforme

Abstract

Glucose, an energy source for cells, also forms the backbone for the creation of ribose and deoxyribose, vital for RNA and DNA synthesis, and is key to the development of necessary lipids and specific amino acids for cell growth. It has been observed that amount of glucose usage corresponds with heightened malignancy, poor prognosis, and increased treatment resistance in cancer cells. It has been observed that modulation of glucose flux and energy supply to tumor cells leads to better cancer control. An innovative method to is the use of 2-deoxy-D-glucose (2-DG), it’s a glucose molecule which has the 2-hydroxyl group replaced by hydrogen. It enters tumor cells preferentially through the same glucose transporters. Once inside, it gets phosphorylated by hexokinase to become 2-deoxy-d-glucose-6-phosphate (2-DG-6-P) which halts further glucose metabolism. This disruption severely depletes ATP in hypoxic tumor cells relying on glycolysis for energy, causing cell death. In areas with ample oxygen where fats and proteins serve as energy substitutes, ATP depletion is less acute, yet 2- DG administration curtails protein translation, hindering proteins vital for cell growth and duplication. 2-DG, also acting as a mannose mimetic, disrupts N-linked glycosylation and induces endoplasmic reticulum (ER) stress, which has shown to inhibit tumor cells' growth. Infusing 2-DG at low doses or metronomically is suggested to enhance cancer control. This case study shows substantial improvements in both radiological outcomes and clinical parameters in a Glioblastoma Multiforme; Grade IV patient by incorporating low dose metronomic 2-DG infusion into the treatment. The patient had undergone surgery followed by radiation and was on Temozolomide therapy. 2-DG disrupts cancer cells' energy metabolism significantly, making them more susceptible to cytotoxic drugs like doxorubicin, cisplatin, and gemcitabine, enhancing radiotherapy effects, particularly in Glioblastoma Multiforme.Malignant gliomas, some of the most resistant tumors, are incredibly heterogeneous with multiple hypoxic regions. 2-DG, due to its ability to penetrate the blood-brain barrier (BBB) and starve hypoxic cancer cells, holds significant potential in glioma treatments.