Cancer cells have finely tuned ‘engines’ that allow them to grow fast in even the most demanding conditions, a leading Cancer Research UK scientists will reveal at a conference1 in Honolulu.
By processing their fuel so effectively – even in the absence of oxygen – cancer cells are able to grow and divide far more quickly than their healthy counterparts.
Prof John Griffiths has identified a key element of cancer’s turbo charged engine. Developing drugs to inactivate the system could be an important way of preventing cancer cells from dividing, bringing a tumour’s growth to a halt.
His research focussed on a gene called HIF-1, which he suspected was crucial to the energy boost. Healthy cells usually only switch on HIF-1 when lacking oxygen – often after damage to the blood supply – setting off systems for keeping cells alive and repairing damaged tissue.
In many cancer cells the HIF-1 gene is permanently switched on. This seems to allow them to survive and grow in the low oxygen conditions that often exist at the centre of a tumour. But Prof Griffiths found that the gene is not only important for keeping cancer cells going in the absence of oxygen – it is also vital for turbo-charging dividing cells by providing them with the energy they need.
Prof Griffiths, who is based at London’s St George’s Hospital, says: “Cancer cells are quite extraordinary really. They manage to optimise their resources so well that even with a crucial part of their energy system missing, they can grow faster than normal cells.
“But this strength also gives us a clear target in terms of new treatments. If we can design drugs to disrupt cancer’s finely tuned engine, we could perhaps draw the growth of tumours to a spluttering halt.”
He studied cancer cells in which the function of HIF-1 had been deliberately destroyed, to see exactly how the gene was helping cells to grow. A highly sophisticated scanning technique called Magnetic Resonance Spectroscopy was used to measure molecules involved in supplying cells with energy.
Cancer cells that lacked HIF-1 had only a fifth of the normal amount of ATP – the main source of fuel for all types of cells. Cancer cells also had low amounts of several molecules used to make ATP. This suggests that without HIF-1, cancer cells lack the means to produce the energy they need.
Surprisingly, although the number of energy molecules was dramatically reduced, the cells were able to grow nearly as quickly as usual. Cancer cells seem to focus their energy consumption on growth and division and can run on much less fuel then their normal counterparts.
Prof Griffiths adds: “Since HIF-1 is key to cancer’s finely tuned abilities, it could become an important target for future anti-cancer drugs. The gene is normally only switched on in highly specific conditions – in the absence of oxygen – so drugs that block its function should attack a tumour selectively while leaving healthy tissue unharmed.”
Sir Paul Nurse, Interim Chief Executive of Cancer Research UK, says: “Learning how cancer cells provide themselves with the energy they need to grow and divide will help us discover treatments which will disrupt the process. Drugs that attack features of cancer that are not shared by healthy tissue might be more effective and have fewer side-effects than those currently available.”