Scientists have identified a new method of killing pancreatic cancer cells, by severing connections to the energy generator that fuels calcium pumps on the cell’s surface.
In functioning cells, calcium is normally beneficial as it controls numerous cell functions. Calcium levels are tightly controlled and normally kept at very low levels as prolonged elevations can cause cell death.
The tight control of calcium is achieved by calcium pumps on the cell’s surface that uses chemical energy to pump calcium out of the cell. A team of researchers at the University of Manchester discovered that switching off the cancer cell’s energy supply causes these pumps to fail. This causes calcium to flood the unhealthy cell.
Dr Jason Bruce, from the Division of Cancer Sciences at the University of Manchester, who led the research, said: “Pancreatic cancer has some of the worst survival statistics and is notoriously resistant to standard treatments.
“Therefore, identifying potential weaknesses of pancreatic cancer cells that could be exploited to selectively kill them – essentially finding their ’Achilles Heel’ – must remain a central research strategy if we are to tackle this devastating disease.”
Funded by the UK charity, Pancreatic Cancer Research Fund, the study identified that pancreatic cancer cells have a unique way of extracting energy from sugar to fuel their calcium pumps. These cells use a specific enzyme called PKM2. Researchers found high levels of this enzyme in tumours compared to the healthier surrounding tissue.
The initial approach, taken by the scientists, targeted the machinery responsible for making PKM2 protein, which eventually leads to a dramatic reduction or “knock-down” of PKM2 within the cancer cells. The second approach used a naturally occurring PKM2 blocker, called shikonin, which stops PKM2 from working. Shikonin was originally extracted from the dried roots of the Arnebia plant, which has been used in traditional Chinese medicine.
“Although shikonin proved to be very effective in the laboratory, it may have additional side effects around the body making it less useful in patients.
“Therefore, we aim to design new drugs that selectively target this process to selectively kill pancreatic cancer cells, while leaving healthy cells that rely on alternative energy sources relatively intact.” explains Dr Bruce.