Food For Thought: Dietary Effects on Tumour Metabolism

Thanks to our deeper understanding of the underlying biology and molecular mechanisms that govern cancer, we are gaining important ground in tackling the myriad mediators of this disease.

Research continues to unravel the complex interactions and interplay between mutated cells and their surrounding biological landscape, stromal cells and inflammatory cells, and extracellular matrix proteins as key components of the tumour microenvironment, and the many socioeconomic factors that make up the macroenvironment.

Delving into the tumour microenvironment, dietary interventions have been shown to change metabolite levels which can influence cancer cell metabolism to alter tumour growth. Over the past decade, in particular, we have gained molecular insights into how diet can affect this disease, where restricting calories may put the brakes on cancer growth, and excessive calorie intake could act as an accelerator of disease progression.

Diet as an anti-cancer ‘co-worker’

Mounting evidence points to the influence of fasting or fasting-mimicking diets (FMDs) on a range of alterations in growth factors and in metabolite levels that can ultimately reduce the capacity of cancer cells to adapt, survive, and grow.

In a peer-reviewed article (Nat Rev Cancer. 2018 Nov;18(11):707-719), the authors discussed the biological rationale for using these diets as an experimental approach in minimising cancer treatment-emergent adverse events as well as more effectively preventing and treating this disease. ,Results from another recent study led by investigators at the Massachusetts Institute of Technology, Cambridge, MA, USA, shed important new light on the subject (Nature. 2021 Nov;599(7884):302-307).

While low glycaemic diets have been suggested to inhibit tumour growth in a preclinical model by lowering blood glucose and insulin levels, alterations in other nutrients have not been well described. At the preclinical level, several diets are now emerging as experimental strategies that might stall cancer growth and even potentiate anticancer medicines in combination with standard therapies.

Lien and colleagues sought to achieve a better understanding of how diet can alter tumour metabolite availability and influence cancer cell metabolism to affect growth. They studied the molecular activity of a low-calorie diet and a ketogenic diet and how they affect tumour progression in PDX1-cre mouse models of pancreatic cancer.

While both diets led to a similar reduction in blood-glucose levels, they discovered that only the calorically restricted diet impaired the growth of specific tumours. By measuring the availability of fatty-acid molecules in the plasma component of blood and in the tumours, the MIT team discovered that in the calorie-restricted mice, lipid levels were reduced, but increased in mice on the ketogenic diet. This observation points to the role of certain fatty acids in the deceleration of cancer growth.

In summary, a ketogenic diet is not and should not be considered for everyone. Only a deep understand of the specific cancer metabolism coupled with the patient's BMI should offer guidance to nutritionists in this field.