Almost every cell in our body is powered by a sugar molecule called glucose. To use glucose as fuel, cells have to break it down into bite-size chunks. And these bite-size chunks help cells function properly.

Cancer cells grow and multiply quickly, which means they need a lot of fuel. And they too rely on glucose to survive.

That’s why scientists have been investigating what happens to cancer cells when they’re starved of glucose. Even though some studies have found that limiting glucose can stop cancer cells from growing, there’s no way to stop cancer cells from taking up glucose in a person without also starving their healthy cells.

Luckily, the human body can use more than one type of sugar. And cancer cells sometimes make and process energy differently to healthy cells. Researchers at the Cancer Research UK Beatson Institute in Glasgow have been looking at how different types of sugar affect growing cancer cells. And in new research, published today in Nature, they’ve uncovered how a molecule like glucose, called mannose, might interfere with cancer cells’ energy supplies.

Stunting tumour growth

Mannose is part of the same family as glucose, sharing a similar molecular shape. So, the team were interested to see what happened when cells growing in the lab were also given mannose.

They studied the inner workings of different types of cancer cells and found that mannose didn’t stop glucose being taken up by the cells, but it did stop them growing. They realised that mannose might be interfering with the way cancer cells break down glucose, stalling their growth.

To find out more, the team monitored the effects of feeding mannose to mice with cancer. Pancreatic cancers, skin cancers and lung cancers all stopped growing when the mice were given mannose supplements three times a week. There also seemed to be no effect on healthy cells.

“Taking mannose did not significantly affect the weight or health of the mice,” says Professor Kevin Ryan, who led the research.

“However, our study didn’t do a detailed analysis of every tissue, so it is not certain that mannose is completely safe.”

The study also looked at other sugars but found that mannose was the most effective at slowing the growth of tumours.

Mannose boosted how well chemo worked in mice

The team also found that mannose boosted cancer cell death when taken alongside chemotherapy.

Mice who were given chemotherapy and mannose together lived longer than those who received no treatment or just chemo or mannose alone. “We were interested to see if mannose enhanced chemotherapy treatment,” says Ryan, “We found that using chemotherapy and mannose separately did reduce the tumour size but using them together had a greater effect and increased life expectancy.”

Mannose supplements

This study offers fascinating insight into how interfering with the way cells make and use sugar could one day treat cancer. But Ryan is clear that it’s certainly not recommended for patients to start taking mannose based on these findings.

While there is promise for future treatments involving mannose, it would be very inadvisable for cancer patients to start using it now.

– Professor Kevin Ryan, lead author

“My worry is that mannose can be bought in tablet form over the counter in pharmacies and health food shops,” he says. “At the moment it can be used to treat urinary tract infections (UTIs) and relieve symptoms for people with carbohydrate deficiencies.”

Despite it being used in these specific cases, mannose hasn’t gone through the appropriate clinical trials and testing to be sure it’s safe to give to people with cancer. Only then could researchers plan to take on the bigger challenge of running trials to see if it would make a better cancer treatment than what’s already available.

“While there is promise for future treatments involving mannose, it would be very inadvisable for cancer patients to start using it now,” says Ryan. “Cancer patients taking mannose for a long period of time that are likely to have weakened immune systems from cancer treatment are not the same as people using mannose in the short-term for UTIs.”

Mannose research is still early stage

The future role of mannose in cancer patients’ treatment isn’t clear. Because of the effects they saw in mice who took mannose and chemo together, Ryan says he doesn’t imagine it as something that can directly treat cancer on its own. Instead, he predicts mannose could act as more of a side kick to existing treatment.

“We think mannose could be the difference between having a small percentage of the tumour leftover after chemotherapy compared to having no residual tumour leftover at all,” he says.

The future of mannose

Before mannose can move to clinical trials, more research needs to be done in the lab.

Even though this study suggests mannose has the potential to slow growing tumours, the research is still at a very early stage. And we can’t presume that the same effects will happen in people. This research also focused on mice with only a small number of tumour types. Ryan and his team now want to see if the same effects happen in mice with other types of cancer.

“We want to find out what tumour cell lines respond to mannose and which don’t,” he says.

Although there is still a long way to go, the study shows promise in managing tumour growth. And if it’s successfully tested in rigorous clinical trials, mannose could have a part to play in improving treatment for some cancer patients in the future.

Lily

Reference

Gonzalez, P.S et al. (2018) Mannose impairs tumour growth and enhances chemotherapy. Nature. DOI: https://doi.org/10.1038/s41586-018-0729-3


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