Killing pancreatic cancer may be as easy as cutting the power supply –– at least if you trust a new study from the University of Manchester’s Cancer Research Centre, where scientists have successfully induced local “power outages” in samples of cancerous tissue. If applicable on a larger scale, the treatment method could represent a significant step toward eradicating one of our most aggressive types of cancer.
Despite numerous advances in oncological diagnosis and treatment, pancreatic cancer is typically accompanied by an abysmal prognosis. One of the main obstacles physicians face when treating the disease is the constant risk of harming surrounding tissue with highly toxic radiation or chemotherapy. For this reason, it can be difficult to deliver a dose high enough to quell the tumor growth.
"Pancreatic cancer is one of the most aggressive and deadly cancers. Most patients develop symptoms after the tumor has spread to other organs,” Jason Bruce, lead researcher of the current study, said in a press release. “Clearly a radical new approach to treatment is urgently required.”
Bruce and his colleagues’ study, which is published in this month’s issue of The Journal of Biological Chemistry, describes an innovative new treatment method that may allow oncologists to circumvent the treatment delivery problem altogether. Rather than killing the cancer with cytotoxic drugs, the new method targets the underlying metabolic process whereby the tumor growth sustains itself. “We wanted to understand how the switch in energy supply in cancer cells might help them survive," Bruce explained.
All cellular activity relies on two internal “power generators” –– mitochondria and glycolysis. For the vast majority of cells, mitochondria generates 90 percent of the energy supply. But in pancreatic cancer cells, this burden falls on glycolysis.
The team found that, by blocking this power supply, they were able to induce cell death in samples taken from human pancreatic tumors. Impaired glycolysis cuts off the cancer cell’s so-called ATP fuel, which consequently leads to a deleterious calcium buildup. "It looks like glycolysis is the key process in providing ATP fuel for the calcium pump in pancreatic cancer cells,” Bruce explained. “Although an important strategy for cell survival, it may also be their major weakness.”
Glycolysis: The Future of Targeted Drug Delivery?
This type of glycolysis restriction figures prominently in a number of recent research efforts. In a study published earlier this year, researchers from the University of Leuven in Belgium showed how certain molecules may be used to block this energy supply. Aside from cancer, the method may also be used to treat inflammatory diseases and age-related macular degeneration.
"These findings will certainly of great interest to the pancreatic cancer research community, and we'd be keen to see how this approach progresses,” said Maggie Blanks of the Pancreatic Caner Research Fund. “Finding weaknesses that can be exploited in this highly aggressive cancer is paramount, so we want to congratulate the Manchester team for their discovery."
Source: Andrew D. James; Oihane Erice; Jason I. E. Bruce. Glycolytic ATP Fuels the Plasma Membrane Calcium Pump Critical for Pancreatic Cancer Cell Survival. The Journal of Biological Chemistry, December 2013