Scientists from The University of Manchester -- part of Manchester Cancer Research Centre believe they have discovered a new way to make chemotherapy treatment more effective for pancreatic cancer patients. Pancreatic cancer is an aggressive cancer with poor prognosis and limited treatment options and is highly resistant¹ to chemotherapy and radiotherapy.

 

But researchers believe they have found an effective strategy for selectively killing² pancreatic cancer while sparing healthy cells which could make treatment more effective.

 

Dr Jason Bruce, from the Physiological³ Systems and Disease Research Group, who led the research, said: "Pancreatic cancer is one of the most aggressive and deadly cancers. Most patients develop symptoms after the tumour⁴ has spread to other organs. To make things worse, pancreatic cancer is highly resistant to chemotherapy and radiotherapy. Clearly a radical⁵ 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 research, published in The Journal of Biological Chemistry this month, found pancreatic cancer cells may have their own specialised energy supply that maintains calcium⁶ 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 plasma⁷ membrane⁸.

 

This calcium pump, known as PMCA, is fuelled using ATP -- the key energy currency for many cellular⁹ processes.

 

All cells generate energy from nutrients¹⁰ using two major biochemical energy "factories," mitochondria（线粒体） and glycolysis（糖酵解）. 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.

 

Scientists used cells taken from human tumours¹¹ and looked at the effect of blocking each of these two energy sources in turn.

 

Their study, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), National Institute of Health Research (NIHR) Biomedical Research Centre and AstraZeneca, shows that blocking mitochondrial metabolism¹² had no effect. However, when they blocked glycolysis, they saw a reduced supply of ATP which inhibited¹³ the calcium pump, resulting in a toxic¹⁴ calcium overload¹⁵ and ultimately cell death.

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