Cancer diets for cancer patients: Lessons from mouse studies and new insights from the study of fatty acid metabolism in tumors

Abstract

Specific diets for cancer patients have the potential to offer an adjuvant modality to conventional anticancer therapy. If the concept of starving cancer cells from nutrients to inhibit tumor growth is quite simple, the translation into the clinics is not straightforward. Several diets have been described including the Calorie-restricted diet based on a reduction in carbohydrate intake and the Ketogenic diet wherein the low carbohydrate content is compensated by a high fat intake. As for other diets that deviate from normal composition only by one or two amino acids, these diets most often revealed a reduction in tumor growth in mice, in particular when associated with chemo- or radiotherapy. By contrast, in cancer patients, the interest of these diets is almost exclusively supported by case reports precluding any conclusions on their real capacity to influence disease outcome. In parallel, the field of tumor lipid metabolism has emerged in the last decade offering a better understanding of how fatty acids are captured, synthesized or stored as lipid droplets in cancers. Fatty acids participate to cancer cell survival in the hypoxic and acidic tumor microenvironment and also support proliferation and invasiveness. Interestingly, while such addiction for fatty acids may account for cancer progression associated with high fat diet, it could also represent an Achilles heel for tumors. In particular n-3 polyunsaturated fatty acids represent a class of lipids that can exert potent cytotoxic effects in tumors and therefore represent an attractive diet supplementation to improve cancer patient outcomes.

Introduction

Today, cancer is still the second leading cause of death worldwide despite the fact that 30–50% of cancers are preventable according to the World Health Organization. In 2018, the World Cancer Research Fund/American Institute for Cancer Research listed food habit recommendations among the factors decreasing the risk of cancer development. Human diet should be mainly composed of whole grains, vegetables, fruits and beans instead of red meat and ultra-processed foods rich in fat, starch and sugars. Alcoholic beverages and sugar-sweetened drinks are also to be avoided [1,2]. The well-known traditional Mediterranean diet appears to fit within these recommendations. Indeed, eating habits of populations bordering the Mediterranean Sea have received a lot of attention during the past decades for their health benefits. This diet is characterized by a generous intake of whole grains, nuts, seeds, vegetables and fruits. Fish is preferred to processed meat and olive oil is the major source of fat. The favorable health effects on cancer prevention are associated with the presence of short-chain fatty acids, antioxidants and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) [3,4]. Lately, a northern substitute to the Mediterranean diet, the Nordic diet, has also come under scrutiny [5]. Its composition, although very similar, is characterized by the presence of rapeseed oil rather than olive oil. Both oils have roughly the same amounts of monounsaturated fatty acids (MUFAs) but rapeseed oil contains less saturated fatty acids (SFAs) and more PUFAs [6]. The two diets are considered as healthy regional diets and offer similar protective effects against cancer [7].

Although not all studies are totally convincing, there is an extensive literature highlighting the strong link between diet and cancer prevention [[8], [9], [10]]. One area that is less studied but is attracting more and more attention is the effect of diet on cancer treatment with or without additional therapies, which will be detailed in this review.