Triple-negative breast cancers present a difficult problem. Most existing therapies for breast cancer target hormone receptors on the cell surface to inhibit cell division. As such, breast cancers that lack these receptors, known as triple-negative cancers, are harder to treat. Physicians need more pharmaceutical options for treating these cancers.
One promising molecule is 2-Deoxy-D-Glucose, which takes advantage of cancer cells’ altered metabolism. Some types of cancer cells depend on glycolysis as their source of energy, rather than oxidative phosphorylation, and so require more glucose than normal cells, which depend on oxidative phosphorylation for energy. Interestingly, 2-Deoxy-D-glucose is a toxic glucose analog that enters cells through normal glucose transporters. The toxicity should be more impactful to cancer cells than to normal cells because of the increased rate of uptake.
One Team’s Investigation
Recently, a team of researchers in Dublin tested 2-Deoxy-D-glucose’s effectiveness at treating breast cancer. They hypothesized that if 2-Deoxy-D-glucose worked as expected, then it should be more toxic to more aggressive, metabolically active cancers than less aggressive ones.
They tested two breast cancer cell lines, Hs578T, and its more aggressive variant, Hs578Ts(i)8. 2-Deoxy-D-glucose reduced the ability of the breast cancer cells to spread and migrate in vitro. The more aggressive cell line was more affected.
Normally when epithelial cells such as breast cancer travel through the blood or lymph system, they undergo apoptosis. Hence, cancer cells must have resistance to apoptosis in order to metastasize. The researchers tested the lines’ resistance to apoptosis. 2-Deoxy-D-glucose reduced the ability of the aggressive cell line to metastasize, but not the less aggressive one. Further evidence also suggests that the cancer stem cells present were directly affected by 2-Deoxy-D-Glucose treatment, in both cell lines.
Therefore, these results suggest that 2-Deoxy-D-glucose has the potential to treat triple-negative breast cancer, particularly the more aggressive variant in this study. Further studies may have a positive impact on developing treatments for the most aggressive and difficult to treat triple-negative breast cancers.
O’Neill S, Porter RK, McNamee N, et al. 2-Deoxy-D-Glucose inhibits aggressive triple-negative breast cancer cells by targeting glycolysis and the cancer stem cell phenotype. Sci Rep. 2019. 9:3788. doi: 10.1038/s41598-019-39789-9. PMID: 30846710.