Researchers have discovered a way to target cancer cells’ nutritional needs, which could lead to a new way to treat the disease.
Cancer cells adapt their metabolism to support growth and survival. Consequently, this leads to various dependencies and vulnerabilities that could be targeted by therapy. Several factors contribute to these metabolic alterations, including genetic alterations in the tumour and tumour environment. Recently, attention has shifted to the role of serine metabolism in supporting cancer cell growth. Serine and glycine play key roles in a number of important processes. Several studies in mice and cancer cells have specifically shown that cancer growth can be reduced in response to diets lacking serine. However, these results have been variable as some cancer cells, particular those with KRAS mutations, are efficient at generating their own serine.
Exploiting dietary demands
In this study, published in Nature Communications, researchers showed that inhibition of PHGDH (the first step in the serine synthesis pathway) cooperated with serine and glycine depletion to inhibit cancer metabolism and growth. Moreover, in vitro inhibition of PHGDH combined with serine starvation resulted in defective global protein synthesis. Additionally, the combination of diet and inhibitor showed therapeutic efficacy against tumours that were resistant to diet or drug alone.
This data supports the therapeutic potential of combining dietary serine and glycine restriction with a small molecule inhibitor of PHGDH. This combination may prove particularly effective for tumours carrying other genetic alterations that lead to resistance to dietary serine depletion.
Professor Karen Vousden, Cancer Research UK’s Chief Scientist, stated:
“The idea of being able to develop dietary interventions, based on the understanding of mechanisms behind how changes in nutrients affect tumours, has the potential to unlock a powerful way to treat cancer.
In the future this could provide a basis for developing a precision medicine approach to diet as a cancer therapy, much as we do with targeted drugs. Personalising each individual’s diet to target the nutritional demands of cancer could, alongside other therapies, give people the best opportunity to respond to treatment.”
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