Radioactive bacteria nuke pancreatic cancer in mice

In the fight against a silent killer, you've got to resort to dirty tactics.

Pancreatic cancer is deadly because it tends to spread, or metastasise, to other parts of the body before symptoms appear. In previous work in mice, Claudia Gravekamp of the Albert Einstein College of Medicine in New York had shown that weakened listeria bacteria colonise tumour tissue but not healthy tissue. What's more, the bacteria seem to home in on the metastatic tumours.

To take advantage of this, her team have now armed the bacteria with a radioactive payload ? attaching the isotope rhenium-188 to the listeria using a type of antibody.

They seeded mice with human pancreatic tumours and then injected them daily with the souped-up bacteria for a week, giving them a week off before four more days of injections. A few days later, there were on average 90 per cent fewer metastatic tumours in this group than there were in untreated mice, and the average weights of original pancreatic tumours had decreased by 64 per cent.

A week later, the animals' livers and kidneys had completely cleared the radioactive bacteria from their systems, with no damage to either organ.

Gravekamp thinks the radiation affected metastatic tumours most because cells there were still rapidly multiplying, leaving their chromosomes more open to damage than those in healthy tissues or in the original tumour. The bacteria also play a part by producing reactive oxygen molecules that again damage the tumour's DNA.

If the approach progresses to clinical trials, says Gravekamp, the idea would be to cut out the original tumour, then clear the rest with radioactive listeria. The next step is to test this strategy in mice, as well as other isotopes such as phosphorus-32, which could be incorporated into the cell wall of the bacterium, removing the need for the antibody tether.

"The results from this fascinating approach are encouraging, but we can't tell whether it would be safe or effective until trials are carried out in patients," says Nell Barrie, science communications manager at Cancer Research UK. "But progress is urgently needed, so new approaches like this deserve further investigation."

Journal reference: PNAS, DOI: 10.1073/pnas.1211287110

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