Microbeams point to future of radiotherapy

Zapping cancer cells with a futuristic microbeam – one of only two fully operational in the world – could pave the way for significant advances in radiotherapy, scientists from Cancer Research UK report¹.

Researchers used the pioneering technology to fire particles of radiation one at a time at individual cancer cells, providing a startling new picture of how cells respond to treatment.

They found particles of radiation can kill many more cells than they hit directly, by causing zapped cells to send out suicidal signals to their neighbours. Understanding this ‘bystander effect’ may help to make radiotherapy more potent against tumours or less damaging to healthy tissue.

Cancer Research UK scientists at the Gray Cancer Institute were among the first to develop the microbeam, which fires a beam of helium ions just a thousandth of a millimetre wide. In the new study, they grew brain cancer cells that they knew were highly resistant to conventional radiotherapy in culture dishes and targeted single cells with the beam.

Hitting just one cell among 1,200 sent a significant proportion of cells in the dish on the path to suicide and by targeting just a few cancer cells, researchers were able to trigger large-scale waves of cell death.

Cancer Research UK’s Dr Kevin Prise, leading the research at the Gray Cancer Institute, says: “We used to assume that the only way to kill cancer cells with radiotherapy was to hit every one of the cells in the tumour with a fatal dose of radiation. Now we’re finding that it’s possible to hit just a handful of cells with much lower doses and let the cells’ natural suicide machinery do the rest.”

“Our discovery has important implications both for optimising the effectiveness of radiotherapy and for protecting healthy tissue from its effects.

“If we could enhance the bystander effect within tumours, we could develop much more effective systems of radiotherapy, perhaps using lower doses to reduce side effects. But of course it also means that even very low doses of radiation may be doing more damage to normal cells than we’d thought, so we’ll have to look for ways of protecting healthy tissue more effectively.”

Scientists think the bystander effect occurs as part of a natural protective mechanism designed to prevent cells from growing and dividing if they have suffered genetic damage. If they’re hit by low doses of radiation, cells not only decide to commit suicide, but release a cocktail of chemical messengers telling their neighbours to die as well.

In the new study, they found the bystander effect relies on a molecule called nitric oxide, which plays an important role in a cell’s response to stress. When the amount of nitric oxide was reduced, cells targeted with radiation stopped sending out suicidal signals.

Dr Prise explains: “Nitric oxide is a molecule cells produce to help them react to stressful situations and seems to be important in their decision to send out suicidal signals when they’re hit by radiation.

“Making sure that there are high amounts of the molecule produced within tumours may be essential to optimise the bystander effect and improve treatments.”

He adds: “We also think the mechanisms involved in the bystander effect might be different in healthy and cancerous tissue, so it might be possible to develop drugs that protect normal tissue from radiotherapy while leaving cancer cells more vulnerable.”

Professor Robert Souhami, Cancer Research UK’s Director of Clinical and External Affairs, says: “It’s only with our investment in this fantastic technology – which allows scientists not just to target individual cells, but sub-compartments of cells – that we’ve been able to uncover the minute details of how cells respond to radiation.

“Updating clinical radiotherapy by plugging in our modern knowledge of the way cells communicate and behave in response to radiation injury could lead to an extremely important advances, with the potential both to improve cancer treatment and to reduce side effects.”

ENDS

1. Cancer Research63 (23)

Note to Editors:

Researchers assessed the number of cells beginning the process of cell suicide by counting the number of micronuclei – shattered pieces of nucleus characteristic of dying cells.