Amino Acids in Diet Could Be Key to Starving Cancer

Cancer cells have an unnatural appetite for certain amino acids—nonessential amino acids that healthy cells produce themselves, usually in amounts sufficient for ordinary metabolism. If cancer cells are denied these amino acids, they are weakened. They grow and proliferate more slowly. It is possible, moreover, that they could be more vulnerable to conventional cancer treatments, such as chemotherapy and radiotherapy.

A controlled diet that restricts amino acid could be used to against cancer is being explored by a team of Cancer Research UK scientists. Working with endogenous tumor mouse models, these scientists found that removing the amino acids serine and glycine from the diet slowed the development of lymphoma and intestinal cancer.

Another finding from the study is especially encouraging. Serine and glycine deprivation appears to leave tumors more susceptible to chemicals in cells called reactive oxygen species, the very chemicals that become more abundant in cells when chemotherapy and radiotherapy are administered.

Additional details appeared April 19 in the journal Nature, in an article entitled “Modulating the Therapeutic Response of Tumours to Dietary Serine and Glycine Starvation.” The article noted that previous studies showed that restricting dietary serine and glycine can reduce tumor growth in xenograft and allograft models. By working with genetically engineered mouse models of intestinal cancer (driven by Apc inactivation) or lymphoma (driven by Myc activation), the Cancer Research UK scientists hoped to extend diet therapy research to “more clinically relevant autochthonous tumors.”

“Transferring mice from normal chow diet to experimental diets 60–80 days after birth showed that [a serine- and glycine-free] diet significantly extended survival in these models carrying pre-malignant lesions,” wrote the article’s authors. “The increased survival following dietary restriction of serine and glycine in these models was further improved by antagonizing the anti-oxidant response.”

The article also observed that serine and glycine deprivation may not be effective in all cancers.

“Disruption of mitochondrial oxidative phosphorylation (using biguanides) led to a complex response that could improve or impede the anti-tumour effect of serine and glycine starvation,” the article noted. “Notably, Kras-driven mouse models of pancreatic and intestinal cancers were less responsive to depletion of serine and glycine, reflecting an ability of activated Kras to increase the expression of enzymes that are part of the serine synthesis pathway and thus promote de novo serine synthesis.”

Essentially, the diet was less effective in tumors with an activated Kras gene, such as most pancreatic cancer, because the faulty gene boosted the ability of the cancer cells to make their own serine and glycine. Being aware of such effects could help clinicians select which tumors could be best targeted by diet therapy.

“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said Oliver Maddocks, Ph.D., the lead author of the Nature paper and a Cancer Research UK scientist at the University of Glasgow.

A Cancer Research UK spokesperson added that clinical trials could show whether a specialized diet that lacks serine and glycine would be safe and help slow tumor growth in people. Additional research could also work out which patients would be most likely to benefit, depending on the characteristics of their cancer.

“This kind of restricted diet would be a short-term measure and must be carefully controlled and monitored by doctors for safety,” cautioned Prof. Karen Vousden, Cancer Research UK’s chief scientist and study co-author. “Our diet is complex, and protein—the main source of all amino acids—is vital for our health and well-being. This means that patients cannot safely cut out these specific amino acids simply by following some form of home-made diet.”