Cancer diets for cancer patients: Lessons from mouse studies and new insights from the study of fatty acid metabolism in tumors☆
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.
Section snippets
Diet composition
Diet integration in the reflection about optimizing cancer patient care is essential. The most obvious rationale comes from the needs for proliferating cancer cells to meet their biosynthetic and bioenergetic requirements. Those may require particular nutrients or larger amounts of regular nutrients when compared with the metabolic needs of healthy cells, even when from the same origin as cancer cells [11]. These specific demands can actually be exploited in order to target cancer cells that
Carbohydrate-restricted diets
Carbohydrate intake was the first to be altered in diets dedicated for cancer patients. It is indeed known since the beginning of the 20th century that cancer cells consume tremendous amounts of glucose and release lactate. Stimulated glycolysis in tumors was even reported to occur in the presence of oxygen by Otto Warburg who thought that mitochondria were dysfunctional in cancer cells [15]. We know today that besides a few exceptions where tricarboxylic acid cycle (TCA) enzymes are mutated,
Protein-targeted diets
Another way to take advantage of cancer metabolism abnormalities is to target some specific amino acids. Indeed, as some amino acids are engaged in metabolic pathways supporting key biosynthetic processes, amino acid-targeted diets could also be relevant in the fight against cancer. The most studied residues, the starvation of which is associated with tumor growth inhibitory effects, are essential amino acids including leucine, lysine and methionine, and non-essential ones including serine,
Fatty acid-orientated diets
Long underestimated, the importance of lipid metabolism in tumor growth is nowadays well accepted. Many recent reviews have highlighted the relevance of targeting lipid metabolism in cancer therapies [[79], [80], [81], [82], [83], [84]]. The term lipid is used to cover a very large family that encompasses a multitude of categories such as fatty acyls, glycerolipids, glycerophospholipids, sphingolipids and sterols [85]. Here below, we will focus on specific issues mainly related to the sources
Concluding remarks
The purpose of this review was to survey the evidence that support how nutrition may interfere with cancer progression, in particular because of the intimate link between metabolism and cancer cell growth and invasiveness. The establishment of a particular diet that would help reducing tumor growth per se or act as an adjuvant to standard therapies appears very attractive. Whether imbalanced diets such as CR or KD, or supplementation of normal diet with n-3 PUFA or a combination of both
Funding
This work was supported by grants from the Fonds de la Recherche Scientifique (F.R.S.-FNRS), the Télévie, the Belgian Foundation against cancer, the J. Maisin Foundation, the Fondation Louvain and an Action de Recherche Concertée (ARC 19/24-096).
References (187)
- et al.
Healthy aspects of the nordic diet are related to lower total mortality
J. Nutr.
(2011) Pyruvate into lactate and back: from the Warburg effect to symbiotic energy fuel exchange in cancer cells, Radiother
Oncol.
(2009)- et al.
Cancer cell metabolism and mitochondria: nutrient plasticity for TCA cycle fueling
Biochim. Biophys. Acta Rev. Canc
(2017) - et al.
Caloric restriction and cancer: molecular mechanisms and clinical implications
Trends Mol. Med.
(2014) - et al.
Regulation of glycolytic enzyme phosphoglycerate mutase-1 by Sirt1 protein-mediated deacetylation
J. Biol. Chem.
(2012) - et al.
Ketolytic and glycolytic enzymatic expression profiles in malignant gliomas: implication for ketogenic diet therapy
Nutr. Metab.
(2013) - et al.
Low ketolytic enzyme levels in tumors predict ketogenic diet responses in cancer cell lines in vitro and in vivo
J. Lipid Res.
(2018) - et al.
Ketogenic diet in the treatment of cancer – where do we stand?
Mol. Metabol.
(2020) - et al.
Prevention of dietary-fat-fueled ketogenesis attenuates BRAF V600E tumor growth
Cell Metabol.
(2017) - et al.
A ketogenic diet reduces central obesity and serum insulin in women with ovarian or endometrial cancer
J. Nutr.
(2018)
Ketogenic diets as an adjuvant cancer therapy: history and potential mechanism
Redox Biol.
Methionine dependency and cancer treatment
Canc. Treat Rev.
Exploiting methionine restriction for cancer treatment
Biochem. Pharmacol.
Greasing the wheels of the cancer machine: the role of lipid metabolism in cancer
Cell Metabol.
Targeting lipid metabolism of cancer cells: a promising therapeutic strategy for cancer
Canc. Lett.
Diverse roles of fatty acid binding proteins (FABPs) in development and pathogenesis of cancers
Gene
Lipid metabolism at the nexus of diet and tumor microenvironment
Trends Canc.
Rapid induction of histone hyperacetylation and cellular differentiation in human breast tumor cell lines following degradation of histone deacetylase-1
J. Biol. Chem.
Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma
Eur. J. Pharm. Biopharm.
Recommendations and Public Health and Policy Implications
Mediterranean diet: prevention of colorectal cancer
Front. Nutr.
Cancer prevention in Europe: the Mediterranean diet as a protective choice
Eur. J. Canc. Prev.
Towards health-promoting and environmentally friendly regional diets a Nordic example
Publ. Health Nutr.
Adherence to a healthy Nordic food index is associated with a lower incidence of colorectal cancer in women: the Diet, Cancer and Health cohort study
Br. J. Nutr.
Nutrition and the prevention of cancer
J. Fam. Health Care
Diet and cancer prevention
Oncogene
Diet and cancer prevention: an overview
Semin. Oncol.
Alternative fuels for cancer cells
Canc. J.
Nutrition basics
Recommandations alimentaires pour la population belge adulte
A framework for examining how diet impacts tumour metabolism
Nat. Rev. Canc.
Restricted calorie ketogenic diet for the treatment of glioblastoma multiforme
J. Child Neurol.
Caloric restriction and cancer
J. Nutr. Sci. Vitaminol.
Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis
PLoS One
Caloric restriction reduces growth of mammary tumors and metastases
Carcinogenesis
Calorie restriction delays the progression of lesions to pancreatic cancer in the LSL-KrasG12D; Pdx-1/Cre mouse model of pancreatic cancer
Exp. Biol. Med.
Effects of calorie restriction and IGF-1 receptor blockade on the progression of 22Rv1 prostate cancer xenografts
Int. J. Mol. Sci.
Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model
Br. J. Canc.
Dose-dependent effects of calorie restriction on gene expression, metabolism, and tumor progression are partially mediated by insulin-like growth factor-1
Cancer Med.
Tumours with PI3K activation are resistant to dietary restriction
Physiol. Behav.
SIRT1 transgenic mice show phenotypes resembling calorie restriction
Aging Cell
Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer
Nat. Commun.
Oncologist nutrient restriction and radiation therapy for cancer Treatment : when less is more
Oncol.
Fasting and cancer treatment in humans: a case series report
Aging
Fasting and differential chemotherapy protection in patients
Cell Cycle
Ketogenic diets for drug-resistant epilepsy ( Review )
Cochrane Database Syst. Rev.
Hepatocellular carcinoma redirects to ketolysis for progression under nutrition deprivation stress
Cell Res.
Cited by (13)
Hypoxia-driven metabolic heterogeneity and immune evasive behaviour of gastrointestinal cancers: Elements of a recipe for disaster
2022, CytokineCitation Excerpt :Downregulation of the enzyme that catalyses this reaction, acetyl-CoA synthetase 2 (ACSS2), is associated with aggressive colorectal cancer [143]. ACC2 converts acetyl-CoA to malonyl-CoA, which, ultimately produce a saturated 16-C palmitate [144]. This functions as the precursor of long chain nonessential FAs and 18-C oleic acid via the reactions catalysed by the endoplasmic reticular enzymes elongases and desaturases [145].
Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects
2021, Cell MetabolismCitation Excerpt :Most of these dietary studies are based on the original idea that reducing tumor supply of major nutrients could limit cancer cell proliferation. Calorie restriction most often through a low carbohydrate content and more recently diets excluding specific amino acids have been investigated (Dierge et al., 2020; Lv et al., 2014). Applications of these approaches in cancer patients, including via the ketogenic diet that makes fat-generating ketone bodies to spare healthy organs, face obvious issues including weight loss, associated fatigue, and weakness together with practical difficulties in implementing these diets in an everyday cancer patient’s life (Dierge and Feron, 2019; Nestle, 2018).
The Antitumor Effects of α-Linolenic Acid
2024, Journal of Personalized Medicine
- ☆
Each author actively participated to the conception of the work, the collection and analysis of the data and the writing of the manuscript. They all have approved the final article.