Killing cancer with sugar

08 December 2018

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The cancer-fighting effects of chemotherapy can be boosted by a dose of sugar, a new study has shown...

Cancers grow out of control. Damage to their DNA means the cells can bypass the checkpoint systems designed to regulate cell division. This leads to chaotic, disorganised growth, producing tumours capable of crushing and bulldozing their way through healthy tissue. Critically, they also rob nearby healthy tissues of access to energy and essential nutrients.

Cancer therapies try to selectively pick off the cancer cells while leaving non-cancerous cells unharmed. To achieve this, scientists ask what makes cancer cells different from normal cells. A good place to start looking is in the metabolism of tumour cells, which often show an increased reliance on the sugar glucose.

Pablo Sierra Gonzalez and his colleagues at the Cancer Research UK Beatson Institute in Glasgow also noticed that another sugar, mannose, affected tumour cell growth, but in an unexpected way: in the presence of mannose, tumour growth was stunted, both in cells grown in the dish and also in experimental animals.

The Glasgow team compared the effects of mannose alone, chemotherapy alone or both agents administered together in mice with a form of colorectal cancer. In animals that received combination treatment, cell death lead to decreased tumour number and volume, and the mice had increased longevity compared to those receiving no treatment or either treatment in isolation.

So how could exposure to a particular sugar lead to increased tumour cell death? Mannose interferes with multiple pathways responsible for energy production and the creation of raw materials inside the cell. It also causes changes in the levels of key proteins involved in cell death in response to a lack of glucose, making it easier to trigger built-in self-destruction programmes. As such, mannose interference with glucose metabolism makes tumour cells more likely to die.

Cells which are most affected by mannose tend to have low levels of a protein called phosphomannose isomerase, which helps initiate mannose breakdown. In patients with colorectal cancer, tumours have low levels of phosphomannose isomerase, suggesting these patients may benefit from mannose treatment.

Before this approach can be applied to humans, scientists must establish its safety. Sierra Gonzalez and his team did not observe any negative effects on the overall health and weight of treated mice. This suggests mannose intake may present a safe way to interfere with tumour cell metabolism to boost the effects of chemotherapy - a spoonful of (the right) sugar may help the medicine go down in the most delightful way!

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