• calorie restriction
• cancer
• diet
• dietary restriction
• fasting
• microbiota
• nutrition
• overweight
• prevention

• Humans
• Neoplasms/prevention & control
• Animals
• Diet, Healthy
• Diet
• Fasting

• Dietary ingredients
• apoptosis
• cell survival
• radioprotector
• radiosensitivity
• radiosensitizer

• Humans
• Radiation-Sensitizing Agents/pharmacology
• Radiation-Sensitizing Agents/therapeutic use
• Oxidative Stress/drug effects
• Oxidative Stress/radiation effects
• Radiation-Protective Agents/pharmacology
• Radiation-Protective Agents/therapeutic use
• Antioxidants/pharmacology
• Signal Transduction/drug effects
• DNA Damage/drug effects
• DNA Damage/radiation effects
• DNA Repair/drug effects
• Radiation Tolerance/drug effects
• Neoplasms/prevention & control
• Diet
• Animals
• Phytochemicals/pharmacology

• OXPHOS
• cancer
• diet
• glycolysis
• oxidative phosphorylation
• the Warburg effect

• Humans
• Neoplasms/diet therapy
• Warburg Effect, Oncologic
• Diet/methods
• Glucose/metabolism
• Lactic Acid/metabolism

• Adipokines
• cancer
• molecular mechanisms
• obesity

• Humans
• Adipokines/metabolism
• Leptin/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• Phosphatidylinositol 3-Kinases/metabolism
• Adipose Tissue/metabolism
• Obesity/metabolism
• Neoplasms

• Cancer
• Drug resistance
• LncRNAs
• Regulatory factor
• Small-molecule drug
• Traditional Chinese medicine
• Warburg effect
• miRNAs

• Calorie restriction
• Cancer prevention
• Dietary restrictions
• Fasting mimicking diet
• Intermittent fasting
• Mediterranean diet

• Humans
• Diet/adverse effects
• Fasting
• Caloric Restriction
• Aging
• Neoplasms/prevention & control

• P01 AG055369 NIA NIH HHS

• cancer epidemiology
• cancer prevention
• cancer therapy
• climate-change ecology
• ecological epidemiology
• evolutionary ecology
• experimental evolution

• Animals
• Humans
• Cnidaria
• Biological Evolution
• Hydra
• Carcinogenesis
• Neoplasms/etiology

• MAVA Foundation
• André Hoffmann
• ANR EVOSEXCAN

• diets
• immune system
• metabolism

• 17605 Italian Association for Cancer Research

• Intermittent energy restriction
• bioinformatics
• breast cancer
• differentially expressed genes
• enrichment analysis
• hub genes
• obesity
• protein–protein interaction network

• Adult
• Animals
• Humans
• Caloric Restriction
• Weight Loss
• Obesity/therapy
• Risk Reduction Behavior
• Colorectal Neoplasms/prevention & control
• Fasting
• Tumor Microenvironment

• R01 CA257807 NCI NIH HHS
• R01 CA250390 NCI NIH HHS
• R01 CA204808 NCI NIH HHS
• R01 DK119783 NIDDK NIH HHS
• T32 CA057699 NCI NIH HHS
• U54 MD012523 NIMHD NIH HHS
• National Institutes of Health

Chemotherapy and radiotherapy are essential components to the management of most solid malignancies. These modalities exert their effects primarily by mediating the DNA damage of malignant cells; however, healthy cells are also damaged by the same mechanisms and can incur acute and late side effects resulting in both morbidity and mortality. Dietary interventions have been shown to reduce cancer growth, progression, and metastasis in many different solid tumor models and they show promise for improving cancer outcomes in early phase clinical studies. Here, we review preclinical and clinical studies that examine how dietary interventions can impact cancer treatment toxicity and efficacy in patients who were undergoing chemotherapy and/or radiotherapy. This information can help clinicians tailor the dietary regimens to patients based on their treatment methods and promote larger clinical trials to test the dietary effects on cancer treatment safety and efficacy.

Chemotherapy and radiotherapy are first-line treatments in the management of advanced solid tumors. Whereas these treatments are directed at eliminating cancer cells, they cause significant adverse effects that can be detrimental to a patient’s quality of life and even life-threatening. Diet is a modifiable risk factor that has been shown to affect cancer risk, recurrence, and treatment toxicity, but little information is known how diet interacts with cancer treatment modalities. Although dietary interventions, such as intermittent fasting and ketogenic diets, have shown promise in pre-clinical studies by reducing the toxicity and increasing the efficacy of chemotherapeutics, there remains a limited number of clinical studies in this space. This review surveys the impact of dietary interventions (caloric restriction, intermittent and short-term fasting, and ketogenic diet) on cancer treatment outcomes in both pre-clinical and clinical studies. Early studies support a complementary role for these dietary interventions in improving patient quality of life across multiple cancer types by reducing toxicity and perhaps a benefit in treatment efficacy. Larger, phase III, randomized clinical trials are ultimately necessary to evaluate the efficacy of these dietary interventions in improving oncologic or quality of life outcomes for patients that are undergoing chemotherapy or radiotherapy.

• K12 CA001727 NCI NIH HHS

• Adipose tissue
• Chemokines
• Obesity
• Prostate cancer

• Adipose Tissue/metabolism
• Adipose Tissue, White/metabolism
• Chemokine CXCL12
• Humans
• Male
• Obesity/metabolism
• Prostatic Neoplasms/metabolism

• R01 CA196259 NCI NIH HHS
• R01 CA228404 NCI NIH HHS

• Breast neoplasm
• caloric restriction
• chemotherapy
• drug resistance
• fasting

Atherosclerosis remains the leading cause of mortality and morbidity worldwide characterized by the deposition of lipids and fibrous elements in the form of atheroma plaques in vascular areas which are hemodynamically overloaded. The global burden of atherosclerotic cardiovascular disease is steadily increasing and is considered the largest known non-infectious pandemic. The management of atherosclerotic cardiovascular disease is increasing the cost of health care worldwide, which is a concern for researchers and physicians and has caused them to strive to find effective long-term strategies to improve the efficiency of treatments by managing conventional risk factors. Primary prevention of atherosclerotic cardiovascular disease is the preferred method to reduce cardiovascular risk. Fasting, a Mediterranean diet, and caloric restriction can be considered useful clinical tools. The protective impact of physical exercise over the cardiovascular system has been studied in recent years with the intention of explaining the mechanisms involved; the increase in heat shock proteins, antioxidant enzymes and regulators of cardiac myocyte proliferation concentration seem to be the molecular and biochemical shifts that are involved. Developing new therapeutic strategies such as vagus nerve stimulation, either to prevent or slow the disease’s onset and progression, will surely have a profound effect on the lives of millions of people.

• caloric restriction
• diet
• endothelial dysfunction
• fasting
• physical exercise
• sympathetic nervous system
• vagus nerve stimulation

Cancer is one of the most frequently diagnosed diseases, and despite the continuous efforts in searching for new and more effective treatments, its morbidity and mortality remain a significant health problem worldwide. Calorie restriction, a dietary manipulation that consists in a reduction of the calorie intake, is gaining attention as a potential adjuvant intervention for preventing and/or fighting cancer. Several forms of energy reduction intake, which includes caloric restriction tout-court, dietary restrictions, and intermittent fasting, are being explored for their ability to prevent or slow down cancer progression. Additionally, another anti-cancer approach being under investigation relies on the use of nutraceuticals known as “Caloric Restriction Mimetics” that can provide caloric restriction-mediated benefits without subjecting the patients to a strict diet. Preclinical in vitro and in vivo studies consistently show that diet modifiers reducing the calorie have impact on tumor microenvironment and cancer metabolism, resulting in reduced growth and progression of cancer. Preliminary clinical studies show that patients subjected to a reduced nutrient/energy intake experience improved outcomes from chemo- and radiotherapy while better tolerating the side effects. Here, we review the state of the art on the therapeutic potential of calorie restriction and of caloric restriction mimetics in preventing or retarding tumor development by modulating a subset of cellular processes. The most recent clinical progresses with caloric restriction mimetics in the clinical practice are also discussed.

• Caloric restriction mimetics
• Drug therapy
• Ketogenic diet
• Tumor microenvironment
• Warburg effect

Background and Purpose. Postexposure onset of dietary restriction (DR) is expected to provide therapeutic nutritional approaches to reduce health risk from exposure to ionizing radiation (IR) due to such as manned space exploration, radiotherapy, or nuclear accidents as IR could alleviate radiocarcinogenesis in animal models. However, the underlying mechanisms remain largely unknown. This study is aimed at investigating the effect from postexposure onset of DR on genotoxicity and genomic instability (GI) induced by total body irradiation (TBI) in mice. Materials and Methods. Mice were exposed to 2.0 Gy of accelerated iron particles with an initial energy of 500 MeV/nucleon and a linear energy transfer (LET) value of about 200 keV/μm. After TBI, mice were either allowed to free access to a standard laboratory chow or treated under DR (25% cut in diet). Using micronucleus frequency (MNF) in bone marrow erythrocytes, induction of acute genotoxicity and GI in the hematopoietic system was, respectively, determined 1 and 2 months after TBI. Results and Conclusions. TBI alone caused a significant increase in MNF while DR alone did not markedly influence the MNF. DR induced a significant decrease in MNF compared to the treatment by TBI alone. Results demonstrated that postexposure onset of DR could relieve the elevated MNF induced by TBI with high-LET iron particles. These findings indicated that reduction in acute genotoxicity and late GI may be at least a part of the mechanisms underlying decreased radiocarcinogenesis by DR.

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the second leading cause of cancer-related mortality worldwide. Processes involved in HCC progression and development, including cell transformation, proliferation, metastasis, and angiogenesis, are inflammation-associated carcinogenic processes because most cases of HCC develop from chronic liver damage and inflammation. Inflammation has been demonstrated to be a crucial factor inducing tumor development in various cancers, including HCC. Cytokines play critical roles in inflammation to accelerate tumor invasion and metastasis by mediating the migration of immune cells into damaged tissues in response to proinflammatory stimuli. Currently, surgical resection followed by chemotherapy is the most common curative therapeutic regimen for HCC. However, after chemotherapy, drug resistance is clearly observed, and cytokine secretion is dysregulated. Various chemotherapeutic agents, including cisplatin, etoposide, and 5-fluorouracil, demonstrate even lower efficacy in HCC than in other cancers. Tumor resistance to chemotherapeutic drugs is the key limitation of curative treatment and is responsible for treatment failure and recurrence, thus limiting the ability to treat patients with advanced HCC. Therefore, the capability to counteract drug resistance would be a major clinical advancement. In this review, we provide an overview of links between chemotherapeutic agents and inflammatory cytokine secretion in HCC. These links might provide insight into overcoming inflammatory reactions and cytokine secretion, ultimately counteracting chemotherapeutic resistance.

• HCC
• chemotherapy
• cytokine
• drug resistance

• Antineoplastic Agents/therapeutic use
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/physiopathology
• Cytokines
• Drug Resistance, Neoplasm
• Humans
• Treatment Outcome

• Amyloid beta peptide
• Autophagy
• Caloric restriction
• Chaperone-mediated autophagy
• Macroautophagy

• FOXP1
• NDRG1
• Prostate cancer
• RAD9

• caloric restriction
• cancer
• duodenum mucosa
• gene expression
• immune response
• metabolic reprogramming
• oncogenic pathways
• telomere maintenance

Pancreatic cancer (PC) is a malignant tumor with high invasiveness, easy metastatic ability, and chemoresistance. Patients with PC have an extremely low survival rate due to the difficulty in early diagnosis. It is estimated that nearly 90% of PC cases are caused by environmental risk factors. Approximately 50% of PC cases are induced by an unhealthy diet, which can be avoided. Given this large attribution to diet, numerous studies have assessed the relationship between various dietary factors and PC. This article reviews three beneficial diets: a ketogenic diet (KD), a Mediterranean diet (MD), and a low-sugar diet. Their composition and impact mechanism are summarized and discussed. The associations between these three diets and PC were analyzed, and we aimed to provide more help and new insights for the prevention and treatment of PC.

• Mediterranean diet
• diet
• ketogenic diet
• low-sugar diet
• pancreatic cancer

• energy balance
• epidemiology
• mortality

• Aged
• Cardiovascular Diseases/mortality
• Cause of Death
• Diet/mortality
• Diet Surveys
• Energy Intake
• Energy Metabolism
• Female
• Humans
• Male
• Neoplasms/mortality
• Proportional Hazards Models
• Prospective Studies
• Spain/epidemiology

• 2017BP00021 Generalitat de Catalunya

• Ageing
• Brain
• Intermittent calorie restriction
• Neurodegeneration
• Neurogenesis
• miRNA

Radioadaptive response (RAR) describes a phenomenon in a variety of in vitro and in vivo systems that a low-dose of priming ionizing radiation (IR) reduces detrimental effects of a subsequent challenge IR at higher doses. Among in vivo investigations, studies using the mouse RAR model (Yonezawa Effect) showed that RAR could significantly extenuate high-dose IR-induced detrimental effects such as decrease of hematopoietic stem cells and progenitor cells, acute radiation hematopoietic syndrome, genotoxicity and genomic instability. Meanwhile, it has been demonstrated that diet intervention has a great impact on health, and dietary restriction shows beneficial effects on numerous diseases in animal models. In this work, by using the mouse RAR model and mild dietary restriction (MDR), we confirmed that combination of RAR and MDR could more efficiently reduce radiogenotoxic damage without significant change of the RAR phenotype. These findings suggested that MDR may share some common pathways with RAR to activate mechanisms consequently resulting in suppression of genotoxicity. As MDR could also increase resistance to chemotherapy and radiotherapy in normal cells, we propose that combination of MDR, RAR, and other cancer treatments (i.e., chemotherapy and radiotherapy) represent a potential strategy to increase the treatment efficacy and prevent IR risk in humans.

• adaptive response
• dietary restriction
• ionizing radiation
• mice
• radiogenotoxicity

• Danio rerio
• calorie restriction
• feed restriction
• gut

• Animal Feed
• Animals
• Eating
• Energy Intake
• Female
• Gene Expression Regulation
• Intestines/anatomy & histology
• Intestines/growth & development
• Male
• Sex Characteristics
• Zebrafish/anatomy & histology
• Zebrafish/growth & development

• DPP-4 inhibitors
• GLP-1 receptor agonists
• insulin
• metformin
• sulfonylureas
• thiazolidinedions

• Diabetes Mellitus, Type 2/drug therapy
• Humans
• Hypoglycemic Agents/administration & dosage
• Hypoglycemic Agents/adverse effects
• Incidence
• Neoplasms/chemically induced
• Neoplasms/epidemiology
• Risk Factors
• Sodium-Glucose Transporter 2 Inhibitors/administration & dosage
• Sodium-Glucose Transporter 2 Inhibitors/adverse effects
• United States/epidemiology

• Biomarkers
• Gene expression
• Inflammation
• Overweight/obese
• Prostate cancer
• Weight loss/maintenance

Cancer incidences are rising globally. Therefore, in order to prevent and treat cancer, understanding cancer pathology is crucial. Tumors reprogram their metabolic phenotype to meet their needs for bioenergy, biosynthesis, and redox control. Alteration of the metabolic pathway has been proposed as the hallmark of cancer and explains the distinction between normal and cancer cells concerning nutrient utilization. Changes in the metabolism of nutrients such as glucose, amino acid, and fatty acid are associated with cancer risk. Luckily, this can be controlled with lifestyle modifications. Improvements in lifestyle behaviors to reduce cancer risks include a healthy diet, calorie restriction, and regular physical activity. This review begins with the understandings of metabolic reprogramming in cancer. Then, there will be evidence on the correlation between lifestyle factors and altered nutrient metabolism suggesting an application of lifestyle intervention for cancer risk reduction.

• Cancer
• Lifestyle
• Metabolism
• Nutrient
• Oncogene

• aging
• caloric restriction
• cardiac aging
• heart failure
• mTOR
• rapamycin

• Cachexia
• cancer
• diet
• ketogenic diet
• nutrition
• nutritionist
• obesity

• Healthful longevity
• Oxidative stress
• Reactive oxygen species

• Aging
• Animals
• Humans
• Longevity
• Mice
• Oxidative Stress
• Reactive Oxygen Species
• Signal Transduction

• R01 HL106511 NHLBI NIH HHS
• R01 HL130848 NHLBI NIH HHS
• R01 HL137368 NHLBI NIH HHS
• R01 HL137405 NHLBI NIH HHS

Dietary interventions have a significant impact on body metabolism. The sensitivity of cancer cells to nutrient and energy deficiency is an evolving characteristic of cancer biology. Preclinical studies provided robust evidence that energy and caloric restrictions could hinder both cancer growth and progression, besides enhancing the efficacy of chemotherapy and radiation therapy. Moreover, several, albeit low-powered, clinical trials have demonstrated clinical benefits in cancer patients. Future research will inform and firmly establish the potential efficacy and safety of these dietary interventions. Here, we review the current evidence and ongoing research investigating the relationship between various dietary restriction approaches and cancer outcomes.

• Caloric restriction
• Cancer
• Energy restriction
• Fasting

• autophagy
• caloric restriction
• cancer
• cancer therapy
• fasting
• metabolism

• Aging/genetics
• Aging/metabolism
• Aging/pathology
• Animals
• Antioxidants/metabolism
• Caloric Restriction/methods
• Diet Therapy
• Drosophila Proteins/genetics
• Drosophila melanogaster/genetics
• Drosophila melanogaster/metabolism
• Longevity/genetics
• Proteomics

• National Natural Science Foundation of China

• Exercise
• aging
• calorie restriction
• cancer risk and progression
• immunity

• T32 GM108563 NIGMS NIH HHS

For the past 100 years, oncologists have relentlessly pursued the destruction of tumor cells by surgical, chemotherapeutic or radiation oncological means. Consistent with this focus, treatment plans are typically based on key characteristics of the tumor itself such as disease site, histology and staging based on local, regional and systemic dissemination. Precision medicine is similarly built on the premise that detailed knowledge of molecular alterations of tumor cells themselves enables better and more effective tumor cell destruction. Recently, host factors within the tumor microenvironment including the vasculature and immune systems have been recognized as modifiers of disease progression and are being targeted for therapeutic gain. In this review, we argue that—to optimize the impact of old and new treatment options—we need to take account of an epidemic that occurs independently of—but has major impact on—the development and treatment of malignant diseases. This is the rapidly increasing number of patients with excess weight and its’ attendant metabolic consequences, commonly described as metabolic syndrome. It is well established that patients with altered metabolism manifesting as obesity, metabolic syndrome and chronic inflammation have an increased incidence of cancer. Here, we focus on evidence that these patients also respond differently to cancer therapy including radiation and provide a perspective how exercise, diet or pharmacological agents may be harnessed to improve therapeutic responses in this patient population.

• caloric restriction
• cancer therapy
• dietary interventions
• host metabolism
• obesity
• radiation

• Beige adipocytes
• Caloric restriction
• Fission
• Fusion
• Mitochondrial biogenesis
• Mitochondrial dynamics
• Mitophagy

• Adipocytes, Beige/physiology
• Adipocytes, White/physiology
• Adipose Tissue/cytology
• Adrenergic beta-3 Receptor Agonists/pharmacology
• Animals
• Body Composition
• Caloric Restriction
• Cell Fusion
• Diet
• Insulin/blood
• Mice
• Mice, Inbred C57BL
• Mitophagy
• Organelle Biogenesis
• Oxygen Consumption
• Primary Cell Culture

• K99 DK110537 NIDDK NIH HHS
• R00 DK110537 NIDDK NIH HHS
• P30 DK120531 NIDDK NIH HHS
• S10 RR019003 NCRR NIH HHS
• R01 DK119627 NIDDK NIH HHS
• R01 DK114012 NIDDK NIH HHS

The complex cellular mechanisms and inter-related pathways of cancer proliferation, evasion, and metastasis remain an emerging field of research. Over the last several decades, nutritional research has prominent role in identifying emerging adjuvant therapies in our fight against cancer. Nutritional and dietary interventions are being explored to improve the morbidity and mortality for cancer patients worldwide. In this review, we examine several dietary interventions and their proposed mechanisms against cancer as well as identifying limitations in the currently available literature. This review provides a comprehensive review of the cancer metabolism, dietary interventions used during cancer treatment, anti metabolic drugs, and their impact on nutritional deficiencies along with a critical review of the following diets: caloric restriction, intermittent fasting, ketogenic diet, Mediterranean diet, Japanese diet, and vegan diet.

• Diet
• caloric restriction
• intermittent fasting
• ketogenic diet
• oncology

Nutrient restriction (NR) decreases the incidence and growth of many types of tumors, yet the underlying mechanisms are not fully understood. In this study, we identified Headcase (Hdc) and Unkempt (Unk) as two NR-specific tumor suppressor proteins that form a complex to restrict cell cycle progression and tissue growth in response to NR in Drosophila. Loss of Hdc or Unk does not confer apparent growth advantage under normal nutrient conditions but leads to accelerated cell cycle progression and tissue overgrowth under NR. Hdc and Unk bind to the TORC1 component Raptor and preferentially regulate S6 phosphorylation in a TORC1-dependent manner. We further show that HECA and UNK, the human counterparts of Drosophila Hdc and Unk, respectively, have a conserved function in regulating S6 phosphorylation and tissue growth. The identification of Hdc and Unk as two NR-specific tumor suppressors provides insight into molecular mechanisms underlying the anti-tumorigenic effects of NR.

The molecular mechanisms underlying nutrient restriction resistance remain unclear. Li et al. find that Hdc and Unk function in the mTOR signaling pathway to restrict tissue growth and cell cycle progression in response to nutrient restriction.

• Drosophila
• Headcase
• Unkempt
• cell cycle progression
• mTORC1
• nutrient restriction
• tissue growth

BACKGROUND: Diabetes mellitus is unfavorably associated with cancer risk. The purpose of this multidisciplinary project was to evaluate a possible association of diabetes mellitus and other comorbidities and their treatment with progression of colorectal cancer. PATIENTS AND METHODS: We investigated the correlation between pathological characteristics and clinical course, including comorbidities in 1004 Czech patients diagnosed and surgically treated for colorectal adenocarcinoma (CRC) between 1999 and 2016. RESULTS: In our data set, CRC patients treated with metformin due to coexisting diabetes mellitus type 2 (T2DM) developed fewer distant metastases which clinically correlates with slower CRC progression. Survival in metformin subgroup was longer, particularly in men with CRC. Osteoporosis may be a negative factor of survival in CRC patients. CONCLUSIONS: Our findings also indicate that aging, higher tumor grade and TNM stage, coexistence of selected endocrine disorders, and metabolic abnormalities may change the tumor microenvironment and impact survival in colorectal cancer, although mechanism of these observations yet to be explained. Patients with diabetes mellitus type 2 treated with metformin may represent the altered microenvironment with specifically tuned metabolic molecular responses and with various epigenetic characteristics. More awareness and increased understanding of the mechanisms underlying the positive effect of metformin on patients' survival could offer insight into new treatment methods and permit more individualized treatment plans.

• Cell Proliferation
• Diet
• Disease Progression
• Hormones/metabolism
• Humans
• Medical Oncology
• Neoplasm Metastasis
• Neoplasms/metabolism
• Neoplasms/pathology
• Risk
• Signal Transduction
• Treatment Outcome

Fasting is deeply entrenched in evolution, yet its potential applications to today’s most common, disabling neurological diseases remain relatively unexplored. Fasting induces an altered metabolic state that optimizes neuron bioenergetics, plasticity, and resilience in a way that may counteract a broad array of neurological disorders. In both animals and humans, fasting prevents and treats the metabolic syndrome, a major risk factor for many neurological diseases. In animals, fasting probably prevents the formation of tumors, possibly treats established tumors, and improves tumor responses to chemotherapy. In human cancers, including cancers that involve the brain, fasting ameliorates chemotherapy-related adverse effects and may protect normal cells from chemotherapy. Fasting improves cognition, stalls age-related cognitive decline, usually slows neurodegeneration, reduces brain damage and enhances functional recovery after stroke, and mitigates the pathological and clinical features of epilepsy and multiple sclerosis in animal models. Primarily due to a lack of research, the evidence supporting fasting as a treatment in human neurological disorders, including neurodegeneration, stroke, epilepsy, and multiple sclerosis, is indirect or non-existent. Given the strength of the animal evidence, many exciting discoveries may lie ahead, awaiting future investigations into the viability of fasting as a therapy in neurological disease.

• cancer
• epilepsy
• fasting
• metabolic syndrome
• multiple sclerosis
• neurodegeneration
• neurological disease
• stroke
• therapy