Nutrient availability a possible factor in tumour growth, study suggests

In newly published research, ​the team highlight findings that not only suggests caloric restriction starve tumours of lipids but also impairs the process that allows them to adapt to this dietary intervention.

“There’s a lot of evidence that diet can affect how fast your cancer progresses, but this is not a cure,”​ says Matthew Vander Heiden, Director of MIT’s Koch Institute for Integrative Cancer Research and senior study author.

“While the findings are provocative, further study is needed, and individual patients should talk to their doctor about the right dietary interventions for their cancer.”​

Experts reacted with caution to the findings with the use of mice models and the focus on only two cancer cell types as reasons for further research.

“The experimental aspects of the study were carried out in mice and warrant further validation in a clinical setting to evaluate the impact of dietary interventions on patient outcomes,”​ says Dr George Poulogiannis, Leader of the Signalling & Cancer Metabolism Team, The Institute of Cancer Research, London.

“The part of the study that involved patients only looked at associations between diets and survival in patients diagnosed with pancreatic cancer.  ​

“This type of study has limitations and cannot tease out cause and effect meaning many other factors could influence a patient’s survival.”​

Study method​

Along with colleagues from the Dana-Farber Cancer Institute in Boston, the study focused on a normal, calorically restricted (CR) and a ketogenic diet (KD) in mice with pancreatic tumours.  Average daily food consumption by weight and calories was measured over three days.

Links between low-carb diets and macronutrients and pancreatic cancer survival rates were also studied in 1,165 patients.

Findings revealed that both diets reduce the amount of sugar available to tumours, but also the CR diet reduced the availability of fatty acids. According to the research team this was likely inhibiting the tumour growth.

Analysis of the human data found the type of fat consumed may influence how patients on a low-sugar diet fare after a pancreatic cancer diagnosis, although the researchers add the data are not complete enough to draw any conclusions about diet’s effect.

“The purpose of these studies isn’t necessarily to recommend a diet, but it’s to really understand the underlying biology,”​ says MIT postdoc Evan Lien is the lead author of the paper, that appears in Nature.

“They provide some sense of the mechanisms of how these diets work, and that can lead to rational ideas on how we might mimic those situations for cancer therapy.”​

However, Paul Pharoah, Professor of Cancer Epidemiology at the University of Cambridge, says, “The authors suggest that their findings are supported by an analysis of survival in individuals with pancreatic cancer.  ​

“However, this component of the study is described very briefly so that it cannot be properly evaluated.  It thus does not provide meaningful evidence that a calorie restriction diet would be of any value in people with pancreatic cancer.”​

Stearoyl-CoA desaturase​

Lipid shortages impair tumour growth as cancer cells need lipids to construct their cell membranes.

When lipids aren’t available in a tissue, cells can make their own, which requires the right balance of saturated and unsaturated fatty acids.

Here, an enzyme, stearoyl-CoA desaturase (SCD) is required, converting saturated fatty acids into unsaturated fatty acids.

The team adds that both diets reduce SCD activity, but mice on the ketogenic diet had lipids available to them from their diet, so they didn’t need to use SCD.

Mice on the calorie-restricted diet, however, couldn’t get fatty acids from their diet or produce their own. In these mice, tumour growth slowed significantly, compared to mice on the ketogenic diet.

Dr Duane Mellor, Registered Dietitian and Senior Teaching Fellow, Aston Medical School, Aston University, adds, “It is important to consider that the tumours were from cells added under the skin of mice and not cancers which are linked to and developed in the actual organs.  ​

“So, although the research mentions pancreatic and lung cancer, these were the type of cell cancers which grew under the skin of mice,” he says.​

“It did this to test the idea that higher levels of insulin and glucose might by linked to increased tumour growth.  It did not look at initial risk of cancer, which might have different dietary risk factors in mice, but more importantly humans.”​

Source: Nature ​

Published online: DOI: 10.1038/s41586-021-04049-2​​

“Low glycaemic diets alter lipid metabolism to influence tumour growth.”​

Authors: Evan Lien et al.