Metabolic therapy: A new paradigm for managing malignant brain cancer

Seyfried, Thomas N.; Flores, Roberto E.; Poff, Angela M.; D’Agostino, Dominic P.; Mukherjee, Purna

doi:10.1016/j.canlet.2014.07.015

Cited by 157 publications

(160 citation statements)

References 226 publications

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“…The lack of effective treatments for patients with malignant glioma requires the design of novel therapeutic strategies that take advantage of common glioma phenotypes, including the altered metabolism of glioma cells (23). It has been postulated that a ketogenic diet, i.e., a diet consisting of high fat, low carbohydrates and adequate protein, may be useful in the treatment of brain tumors (25)(26)(27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

“…It was consistently reported that patients undergoing the KD presented with reduced blood glucose levels and beneficial therapeutic responses, including the transient disappearance of the brain tumor tissue (29)(30)(31). Thus, these case reports, along with numerous anecdotal observations, presented encouraging signs of metabolic reprogramming by the KD, along with the increased efficacy of standard of care treatment for malignant glioma (23,29). This preliminary evidence of the benefit of KD for cancer therapy is currently being validated in ongoing, controlled clinical trials, which include patients with malignant glioma (25).…”

Section: Introductionmentioning

confidence: 85%

“…This so-called Warburg effect (aerobic glycolysis) leads to the increased consumption of glucose and the inability of the affected cells to utilize ketone bodies as an energy source (21). In response to KD, it is hypothesized that tumor cells will starve, or revert to normal mitochondrial activity and respiration, altogether resulting in decreased proliferation and metastatic ability, along with a heightened sensitivity to chemotherapy (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma

et al. 2017

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Abstract. It has been hypothesized that persistent ketotic hypoglycemia represents a potential therapeutic strategy against high-grade gliomas. Perillyl alcohol (POH) is a non-toxic, naturally-occurring, hydroxylated monoterpene that exhibits cytotoxicity against temozolomide-resistant glioma cells, regardless of O6-methylguanine-methyltransferase promoter methylation status. The present study aimed to evaluate the toxicity and therapeutic efficacy of intranasal POH when administered in combination with a ketogenic diet (KD) program for the treatment of patients with recurrent glioblastoma. The 32 enrolled patients were divided into two groups, KD or standard diet, with intranasal POH treatment (n=17 and n=15, respectively). The nutritional status and anthropometric parameters of the patients were measured. Patients that adhered to the KD maintained a strict dietary regimen, in addition to receiving 55 mg POH four times daily, in an uninterrupted administration schedule for three months. Neurological examination and magnetic resonance imaging analysis were used to monitor disease progression. A total of 9/17 patients in the KD group survived and maintained compliance with the KD. After three months of well-tolerated treatment, a partial response (PR) was observed for 77.8% (7/9) of the patients, stable disease (SD) in 11.1% (1/9) and 11.1% (1/9) presented with progressive disease (PD). Among the patients assigned to the standard diet group, the PR rate was 25% (2/8 patients), SD 25% (2/8) and PD 50% (4/8 patients). The patients assigned to the KD group presented with reduced serum lipid levels and decreased low-density lipoprotein cholesterol levels. These results are encouraging and suggest that KD associated with intranasal POH may represent a viable option as an adjunct therapy for recurrent GBM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma

et al. 2017

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“…Recently, CR efficacy has also been demonstrated in relation to radiotherapy, leading to an increase in the sensitivity to radiation-induced cytotoxicity (Champ et al 2013). As alternative to standard chemoÀ/radiotherapy, another type of metabolic therapy has been proposed (ketogenic diet) whose beneficial effects have been demonstrated in the multiform glioblastoma and brain cancer for its antiangiogenic, anti-inflammatory, and antiapoptotic abilities (Seyfried et al 2015). Below we will discuss deeper the association of chemotherapy and dietary restriction in some of the most spread cancers worldwide looking at the benefits deriving from their combination (Fig.…”

Section: The Implication Of Dietary Restriction In Cancermentioning

confidence: 99%

Effects of Dietary Restriction on Cancer Development and Progression

Fanale

Maragliano

Perez

et al. 2017

Handbook of Famine, Starvation, and Nutrient Deprivation

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The effects of caloric restriction on tumor growth and progression are known for over a century. Indeed, fasting has been practiced for millennia, but just recently has emerged the protective role that it may exert toward cells. Fasting cycles are able to reprogram the cellular metabolism, by inducing protection against oxidative stress and prolonging cellular longevity. The reduction of calorie intake as well as short-or long-term fasting has been shown to protect against chronic and degenerative diseases, such as diabetes, cardiovascular pathologies, and cancer. In vitro and in vivo preclinical models showed that different restriction dietary regimens may be effective against cancer onset and progression, by enhancing therapy response and reducing its toxic side effects. Fasting-mediated beneficial effects seem to be due to the reduction of inflammatory response and downregulation of nutrient-related signaling pathways able to modulate cell proliferation and apoptosis. In this chapter, we will discuss the most significant studies present in literature regarding the molecular mechanisms by which dietary restriction may contribute to prevent cancer onset, reduce its progression, and positively affect the response to the treatments.

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“…Recently, as an alternative to standard treatment, metabolic therapies aimed to target metabolic alterations present in all tumor cells and which give a benefit to normal cells have been developed. For example, among the metabolic therapies that improved the prognosis of patients with glioblastoma multiforme and brain cancer, there is the calorie-restricted ketogenic diet (KD-R), which shows antiangiogenic, anti-inflammatory, and anti-apoptotic effects [69].…”

Section: Effects Of Dietary Restrictions On the Main Tumorsmentioning

confidence: 99%

Dietary restriction: could it be considered as speed bump on tumor progression road?

et al. 2016

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Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long-and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models.However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes.

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Metabolic therapy: A new paradigm for managing malignant brain cancer

Cited by 157 publications

References 226 publications

Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma

Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma

Effects of Dietary Restriction on Cancer Development and Progression

Dietary restriction: could it be considered as speed bump on tumor progression road?

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