Beneficial Diets and Pancreatic Cancer: Molecular Mechanisms and Clinical Practice

Zhang, Yang; Zhang, Tao; Yang, Wenbo; Chen, Hongze; Geng, Xinglong; Li, Guanqun; Chen, Hua; Wang, Yongwei; Le, Li; Sun, Bei

doi:10.3389/fonc.2021.630972

Cited by 6 publications

(4 citation statements)

References 195 publications

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“…In the context of PDA, while the KD has been shown to reduce pancreatic tumor growth in vivo in some models (Shukla et al , 2014), other studies revealed no effect of KD alone on PDA tumor growth or animal survival (Hopkins et al , 2018; Lien et al , 2021). Moreover, the limited number of PDA patients studied with this dietary intervention and the lack of long‐term follow‐up make the role of the KD in treating PDA patients unclear (Zhang et al , 2021).…”

Section: Discussionmentioning

confidence: 99%

Ketogenic HMG‐CoA lyase and its product β‐hydroxybutyrate promote pancreatic cancer progression

et al. 2022

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Pancreatic ductal adenocarcinoma (PDA) tumor cells are deprived of oxygen and nutrients and therefore must adapt their metabolism to ensure proliferation. In some physiological states, cells rely on ketone bodies to satisfy their metabolic needs, especially during nutrient stress. Here, we show that PDA cells can activate ketone body metabolism and that b-hydroxybutyrate (bOHB) is an alternative cell-intrinsic or systemic fuel that can promote PDA growth and progression. PDA cells activate enzymes required for ketogenesis, utilizing various nutrients as carbon sources for ketone body formation. By assessing metabolic gene expression from spontaneously arising PDA tumors in mice, we find HMG-CoA lyase (HMGCL), involved in ketogenesis, to be among the most deregulated metabolic enzymes in PDA compared to normal pancreas. In vitro depletion of HMGCL impedes migration, tumor cell invasiveness, and anchorage-independent tumor sphere compaction. Moreover, disrupting HMGCL drastically decreases PDA tumor growth in vivo, while bOHB stimulates metastatic dissemination to the liver. These findings suggest that bOHB increases PDA aggressiveness and identify HMGCL and ketogenesis as metabolic targets for limiting PDA progression.

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Section: Discussionmentioning

confidence: 99%

Ketogenic HMG‐CoA lyase and its product β‐hydroxybutyrate promote pancreatic cancer progression

et al. 2022

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“…This dichotomy suggests that dietary FAω6 to FAω3 ratios may crucially influence inflammatory disease risks, including PC [ 36 ]. Some studies suggest that early life dietary patterns significantly impact cancer development [ 37 , 38 ]. The primary risk factors include a sedentary lifestyle and poor dietary choices, characterized by excessive intake of high-calorie foods and a lack of healthy foods such as those rich in FAω3, antioxidants, and fiber.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, healthy dietary habits, characterized by the consumption of fruits and vegetables rich in fiber, PUFAs, and vitamins, can positively impact human health by reducing chronic inflammation and subsequent DNA damage [ 41 , 42 ]. For example, adhering to a Mediterranean diet, which includes a high intake of fresh fruits, vegetables, legumes, unrefined grains, and olive oil, as well as higher nut consumption, has been shown to be associated with a lower risk of PC [ 38 , 40 ]. Additionally, the intake of PUFAs and their fish sources may have a protective effect against the development of PC.…”

Section: Discussionmentioning

confidence: 99%

Employing Bidirectional Two-Sample Mendelian Randomization Analysis to Verify the Potential of Polyunsaturated Fatty Acid Levels in the Prevention of Pancreatic Cancer

Sha,

Zhu

2024

CIMB

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Polyunsaturated fatty acids (PUFAs), specifically Omega-3 (FAω3) and docosahexaenoic acid (DHA), have been studied for their potential role in modulating pancreatic cancer (PC) risk. Although observational studies suggest a beneficial effect in reducing this risk, their findings are often limited by confounding variables and issues of reverse causation. This study used a two-way two-sample Mendelian randomization (MR) method to test the hypothesized genetic causal relationship between PUFAs and PC risk. Data from an extensive genome-wide association study (GWAS) were analyzed, focusing on FAω3 and FAω6 levels, their ratios, and DHA as variables and PC incidence as outcomes. This relationship was comprehensively evaluated using related MR methods, such as inverse variance weighting (IVW), MR Egger, and weighted median (WM). This study finds a significant negative correlation between FAω3 and DHA levels and PC risk, while FAω6 levels show no significant correlation. Interestingly, the ratio of FAω6 to FAω3 was positively associated with increased risk of PC. Neither the MR Egger nor the MR-PRESSO tests detected significant pleiotropy, nor did the Cochrane’s Q test show significant heterogeneity. Leave-one-out analyzes further confirmed the robustness of these results. Using MR analysis of two samples, this study provides genetic causal evidence that FAω3 and DHA levels reduce the risk of PC, whereas the ratio of FAω6 to FAω3 increases the risk of PC. These insights highlight the potential utility of supplementing FAω3 and DHA or altering PUFAs in developing PC prevention strategies.

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“…Summarily, liver is the glucose and lipid metabolic center that produces ketone bodies, KD has a broad application prospect in the treatment of HCC ( 26 ). In addition, several recent studies have demonstrated that KD effectively inhibited the proliferation of pancreatic by reprogramming cell metabolism, epigenome, and the gut microbiome ( 27 , 28 ). These results suggested that glioma and breast cancer were the most studied cancer types in this field, while hepatocellular carcinoma and pancreatic cancer were the new hotspots and trends.…”

Section: Discussionmentioning

confidence: 99%

Bibliometric and visual analysis in the field of ketogenic diet on cancer from 2012 to 2021

Huang

et al. 2022

Front. Nutr.

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Increasing evidence demonstrated that the ketogenic diet (KD) played a positive effect on cancer treatment. However, no systematic review and bibliometric analysis were conducted in this field. This study aimed to explore the current status, and reveal the potential trends and hotspots to provide a reference for future research. Publications were extracted from the Web of Science Core Collection. CiteSpace (5.6.R3) software and the website of bibliometrics were used for visual analysis. A total of 500 publications with 334 articles and 166 reviews were included, with the timespan of 2012 to 2021. The United States was the most productive country. Majority of the top 10 institutions were from the United States, and Harvard University was the top-contributing institution. The most prolific author and the co-cited author was Thomas N Seyfried from Boston College. The highest cited reference was published in PLoS ONE, authored by Abdelwahab Mohammed G, with 161 citations. Glioma and breast cancer were the most common types of cancer in this field, while hepatocellular carcinoma and pancreatic cancer were the new hotspots. The anti-tumor mechanism of KD mainly focused on regulating metabolism, decanoic acid, oxidative stress, fatty acid oxidation, and cell apoptosis. Additionally, the presence of “chemotherapy” and “radiotherapy” in the keywords indicated that KD combined with anti-tumor research was a topic, while “immunotherapy” has became a recent frontiers. Notably, as a metabolic therapy, KD was deserved more attention in the treatment of hepatocellular carcinoma and pancreatic cancer, and KD combined with immunotherapy was the new hotspot and frontier. Additionally, more molecular studies and high-quality uniformly, randomized, controlled clinical trials are urgently warranted to evaluate the effect of KD in multiple cancers.

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Beneficial Diets and Pancreatic Cancer: Molecular Mechanisms and Clinical Practice

Cited by 6 publications

References 195 publications

Ketogenic HMG‐CoA lyase and its product β‐hydroxybutyrate promote pancreatic cancer progression

Ketogenic HMG‐CoA lyase and its product β‐hydroxybutyrate promote pancreatic cancer progression

Employing Bidirectional Two-Sample Mendelian Randomization Analysis to Verify the Potential of Polyunsaturated Fatty Acid Levels in the Prevention of Pancreatic Cancer

Bibliometric and visual analysis in the field of ketogenic diet on cancer from 2012 to 2021

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