Faculty scientists believe they have discovered a way to make chemotherapy more effective for pancreatic cancer patients. They hope they have now found an effective strategy for selectively killing pancreatic cancer while sparing healthy cells, which will improve the results of treatment. Research leader, Dr Jason Bruce, said:
“Pancreatic cancer is one of the most aggressive and deadly cancers. Most patients develop symptoms after the tumour has spread to other organs. To make things worse, pancreatic cancer is highly resistant to chemotherapy and radiotherapy. Clearly a radical new approach to treatment is urgently required. We wanted to understand how the switch in energy supply in cancer cells might help them survive.”
The study found that pancreatic cancer cells may have their own specialised energy supply that maintains calcium levels and keeps cancer cells alive. Maintaining a low concentration of calcium within cells is vital to their survival and is achieved by calcium pumps on the plasma membrane. These pumps, known as PMCA, are fuelled using ATP, the key energy currency for many cellular processes.
All cells generate energy from nutrients using two biochemical energy ‘factories,’ known as mitochondria and glycolysis. Mitochondria generate almost 90% of the cells’ energy in healthy cells. In pancreatic cancer cells there is a shift towards glycolysis as the major energy source. It is thought that the calcium pump has its own supply of glycolytic ATP, which gives the cancer cells an advantage over normal cells.
Scientists used cells from human tumours and investigated the effects of blocking each energy source in turn. Blocking the mitochondrial metabolism had no effect. However, when they blocked glycolysis they saw a reduced supply of ATP which inhibited the calcium pump. This resulted in a toxic calcium overload and the death of the cell. Dr Bruce added:
“It looks like glycolysis is the key process in providing ATP fuel for the calcium pump in pancreatic cancer cells. Although an important strategy for cell survival, it may also be their major weakness. Designing drugs to cut off this supply to the calcium pumps might be an effective strategy for selectively killing cancer cells while sparing normal cells within the pancreas.””