Eliminating serine in diet may help weaken cancer, new study finds

15 Jan 2021 --- Reducing serine in the body through diet and drug therapy could help “starve” cancer cells, according to a new study funded by Cancer Research UK.

Serine is a non-essential amino acid found in many foods, including eggs, lentils, soybean and chickpeas. Serine can also be made by the body and is one of the building blocks for making proteins. 

The study found reduced tumor cell growth in several different bowel cancer models after restricting serine in the diet of mice alongside a drug that prevents the body from making it endogenously.

The new findings suggest new cancer treatments could be developed that exploit this dietary weakness in tumors. 

Diets tailored to fit
Targeted diets could form part of future treatments, similar to how precision medicine has developed with targeted drugs, according to study lead and Cancer Research UK’s chief scientist Professor Karen Vousden.

“The idea of being able to develop dietary interventions, based on the understanding of mechanisms behind how changes in nutrients affect tumors, has the potential to unlock a powerful way to treat cancer,” she says. 

“Personalizing each individual’s diet to target the nutritional demands of cancer could, alongside other therapies, give people the best opportunity to respond to treatment.” 

Personalizing each individual’s diet to target the nutritional demands of cancer could, alongside other therapies, give people the best opportunity to respond to treatment.The researchers hope that this two-pronged approach could work in a range of cancers, including those with KRAS mutations, and could provide an additional way to tackle the disease alongside current treatments, such as chemotherapy. 

“A tantalizing glimpse” 
Understanding the fundamental biology of cancer through studies is vital for revealing the disease’s true complexity, and can shed light on new treatment avenues, explains Michelle Mitchell, CEO at Cancer Research UK. 

“This research has given us a tantalizing glimpse into how we can turn cancer’s dietary dependencies against it, and we look forward to seeing if the approach works in people.” 

While work remains to be done, people with cancer are not advised to change their diets in light of this new study, flags Martin Ledwick, Cancer Research UK’s head information nurse.

“It’s important to remember that this is still early research in mice and cells. We need to see if this work translates into cancer in humans before testing to see if diet changes are helpful,” he advises. 

Suppressing the body’s serine production
The study led at the Francis Crick Institute in the UK tested a combination of a serine-free diet and a drug called PH755, which prevents cancer cells from making the amino acid, to see if the therapy would be effective at blocking cancer cell growth. 

The researchers inhibited bowel cancer cell growth, both in cell cultures in the lab as well as in organoids – 3D models of tumors that mimic some of the complexity of organs, using this dual approach. 

Critically, in bowel cancer xenografts, where human bowel cancer cells are studied in a mouse model of the disease, they found that the combined approach significantly reduced the tumors’ growth compared to either approach alone. 

Encouragingly, PH755 had few side effects in the animal models. 

If future work shows the limitation of serine in healthy people is possible, then it could lead to a new precision medicine approach to exploiting cancers’ dietary weaknesses as cancer treatments. 

Effective at reducing cancer in miceNumerous studies in mice and cancer cells have shown cancer growth can be reduced in response to diets lacking serine.
The research paper published in Nature Communications builds upon work that found cancer cells to be more dependent on serine than their healthy counterparts due to their accelerated growth.

Numerous studies in mice and cancer cells have shown cancer growth can be reduced in response to diets lacking serine. 

However, results have been variable because some cancer cells are efficient in making their own serine. This is particularly true for those with a KRAS genetic mutation, which is found in several hard-to-treat cancers. 

In other strides to reduce cancer, Vitamin D3 was shown to potentially reduce the risk of developing advanced cancer among adults over the age of 50 without a diagnosis of cancer at baseline.

B3 has also been shown to play a role in protecting the skin against cancer.

Edited by Missy Green