What is 2-Deoxy-D-glucose?

2-Deoxy-D-glucose (2DG) is an analogue of glucose in which a 2-hydroxyl group is replaced by hydrogen. Despite this minor change in its structure, glucose transporters can still carry 2DG into cancer cells disguised as “fake sugar” that they crave intensely.

This alteration prevents sugar from participating in anaerobic glycolysis, the metabolic pathway that breaks down glucose for energy. By interfering with glycolysis, 2DG has the potential to starve cancer cells, which heavily depend on glucose for their rapid growth.

When taken as a powder, 2DG looks almost identical to table sugar, and does not have any taste – other than being a bit gritty – making it a tasteless nutrient-like remedy that can be mixed in water and consumed on an empty stomach.

Previously, 2DG was employed as a non-radioactive tracer that could act as a non-toxic marker in PET scans to visualise the location and relative extent of cancer tissue metabolic activity. But today’s priorities are different. New research has focused on 2DG as a potential agent of anti-cancer therapy.

As cellular energy is produced only through the breakdown (metabolism) of sugar, cancer cells – which are metabolically fast-paced – gobble it up at more than hundred times the rate of normal cells. This phenomenon is referred to as the Warburg effect.

Introduced into the body, 2DG is absorbed by the cancer, but it can’t be metabolised properly – even when cancer cells quickly try to clear it. This causes the sugar metabolism to stall and saps the energy of the cancer cells, reducing their growth and spread, eventually selectively killing them.

The primary strategy behind using 2DG is to “trick” cancer cells into absorbing a substance that hinders their energy production. This allows the body’s natural defenses to combat the tumor more effectively. By leveraging the high glucose dependency of cancer cells, 2DG offers a targeted approach to cancer treatment without significantly affecting normal cells.

References

Overview of 2DG:

• Pelicano, H., Martin, D. S., Xu, R. H., & Huang, P. (2006). Glycolysis inhibition for anticancer treatment. Oncogene, 25(34), 4633-4646. Available at: NCBI

• 2DG as an Anti-Cancer Agent: [H4] 3. Zhang, D., Li, J., Wang, F., Hu, J., & Wang, S. (2014). 2-Deoxy-D-glucose targeting of glucose metabolism in cancer cells as a potential therapy. Cancer Letters, 355(2), 176-183. Available at: NCBI