2-Deoxy-D-Glucose as an Emerging Chemotherapeutic Agent in Cancer Management

Cancer cells have a unique property of uncontrolled growth and thus they require a constant supply of energy. Warburg observed that tumor cells prefer glycolysis even under oxygenic conditions and the process is known as aerobic glycolysis. Hence, cancerous cells show an enhanced glucose-to-lactate conversion rate. As cancerous growth is accompanied by enhanced glucose uptake, this feature is best suited for the management of unwanted cell proliferation by blocking the glucose metabolism of cancer cells. 2-deoxy-D-glucose (2DG), a glucose antimetabolite is considered a competitive inhibitor of glucose transport and glucose phosphorylation. It inhibits the glycolytic pathway primarily due to the inhibition of phosphohexose isomerase by 2-deoxy-D-glucose-6-phosphate (2DG- 6P). Its chemical resemblance to 2-deoxymannose causes interruption in the initial steps of N-linked glycosylation leading to the misfolding of proteins resulting in endoplasmic reticulum stress. In addition to the two properties of 2DG namely, the prevention of glycolysis and selective storage in the tumor cells, there are several other attributes of 2DG apart from the ones mentioned above that make it an attractive target for use as an antitumor agent. Some properties include the capability of inducing autophagy in tumor cells, inhibiting genomic replication as well as mRNA expression of viral genes responsible for Omit the induction of oncogenesis, blocking pathological angiogenesis while being cautious towards established endothelial tubes and prominent anti-metastatic effect. In the present chapter, various aspects of the use of 2DG in cancer management have been discussed.