A new potential anti-cancer agent that inhibits the glycolytic enzyme PGAM1 and thereby tumor growth.
- Targets tumor metabolism by inhibiting glycolytic enzyme and turning off tumor metabolism.
- Inhibition of glycolytic enzyme (PGAM1) by these inhibitors leads to significant reduction in tumor growth.
Treating cancer remains a scourge of the medical world. In 2011, there have been 1.6 million new cancer diagnoses which lead to nearly 600,000 deaths in the U.S. alone. Over a lifetime, 1 in every 2 or 3 Americans will develop cancer, and survival rates vary widely, from as high as 90% in breast cancer to as low as 6% in pancreatic cancers. Even effective cancer therapies have extensive side effects, and new treatments are in high demand.
Cells generate the energy they need to function via glycolysis with cancer cells undergoing rates of glycolysis 200 times greater than normal cells. Glycolytic inhibitors may therefore treat cancer by slowing these abnormal rates of tumor cell glycolysis and "starving" the tumor cells. Emory inventors have designed a novel group of glycolytic inhibitors that down-regulate activity of the enzyme PGAM1, which catalyzes the breakdown of glucose into useable energy. These compounds inhibit PGAM1 activity in leukemia and lung cancer cell lines, and suppress tumor growth in rodent models of cancer to a much greater extent than other glycolytic inhibitors. Cancer cells that exist in low-oxygen conditions or that have dysfunctional mitochondria are often resistant to conventional anti-cancer therapies. Due in part to this resistance, glycolytic inhibitors appear to be particularly effective against these types of cancer cells.
Effectiveness of inhibitors have been determined in both cell based assays and rodent models.