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Developed at the University of Iowa, the drinkable carbon monoxide-infused foam boosted autophagy inhibition therapy in mice and human cells.
Autophagy – the cell’s natural recycling system – is increased in cancer cells, suggesting that inhibiting autophagy might be a way to target cancer cells. Results from almost 20 clinical trials testing autophagy inhibitors have been inconclusive, however.
The Iowa team started the new work after researchers discovered that smokers seemed to do better than non-smokers in two of the previous trials of autophagy inhibitors.
“When we looked at how the smokers did in those trials, we saw an increase in overall response in smokers that received the autophagy inhibitors, compared to (non-smoker) patients, and we also saw a pretty robust decrease in the target lesion size,” said biomedical engineer James Byrne, senior author of a new study on the work.
Smoking is associated with increased levels of carbon monoxide (CO). While the gas is poisonous when inhaled, it can increase autophagy in cells in a way that researchers think might enhance the anti-cancer effect of autophagy inhibitors.
“While we definitely don’t recommend smoking, this suggested that elevated carbon monoxide might improve the effectiveness of autophagy inhibitors. We want to be able to harness that benefit and take it into a therapeutic platform,” said Byrne.
The researcher specialises in making gas-entrapping materials (GEMs) – foams, gels and solids made from safe, edible substances that can be infused with different gas molecules – so the team created a drinkable foam infused with carbon monoxide.
When mice with pancreatic and prostate cancers were fed the carbon monoxide foam and simultaneously treated with an autophagy inhibitor, tumour growth and progression was significantly reduced in the animals. The team also showed that combining carbon monoxide with autophagy inhibitors had a significant anti-cancer effect in human prostate, lung, and pancreatic cancer cells in petri dishes.
Ultimately, Byrne hopes to test this approach in human clinical trials. “The results from this study support the idea that safe, therapeutic levels of CO, which we can deliver using GEMs, can increase the anti-cancer activity of autophagy inhibitors, opening a promising new approach that might improve therapies for many different cancers,” he said.
The research team also included scientists from MIT, Harvard Medical School, the University of Pennsylvania, Rutgers Cancer Institute of New Jersey, the University of North Carolina Wilmington, and Oregon Health and Science University.
The work was published in Advanced Science.
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