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UK researchers find potential new treatment approach for pancreatic cancer

21 December 2013

Scientists from The University of Manchester believe they have discovered a new way to make chemotherapy treatment more effective for pancreatic cancer patients

The researchers believe they have found an effective strategy for selectively killing pancreatic cancer while sparing healthy cells which could make treatment more effective.

The research, published in The Journal of Biological Chemistry this month, found 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 this is achieved by calcium pumps on the plasma membrane.

This calcium pump, known as PMCA, is fuelled using ATP – the key energy currency for many cellular processes.

All cells generate energy from nutrients using two major biochemical energy ‘factories’, mitochondria and glycolysis. Mitochondria generate approximately 90% of the cells’ energy in normal healthy cells. However, in pancreatic cancer cells there is a shift towards glycolysis as the major energy source. It is thought that the calcium pump may have its own supply of glycolytic ATP, and it is this fuel supply that gives cancer cells a survival advantage over normal cells.

The research team used cells taken from human tumours and looked at the effect of blocking each of these two energy sources in turn.

Their findings showed that blocking mitochondrial metabolism had no effect. However, when they blocked glycolysis, they saw a reduced supply of ATP which inhibited the calcium pump, resulting in a toxic calcium overload and ultimately cell death.

Dr Jason Bruce, from the Physiological Systems and Disease Research Group who led the research, said: “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.”

Maggie Blanks, CEO of the Pancreatic Cancer Research Fund said: “Finding weaknesses that can be exploited in this highly aggressive cancer is paramount, so we want to congratulate the Manchester team for their discovery."

The study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), Central Manchester Foundation Trust (CMFT)/National Institute of Health Research (NIHR) Manchester Biological Research Centre and AstraZeneca.

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