145: A No-Carbohydrate Diet Significantly Delays Prostate Cancer Growth in an Animal Model

Freedland, Stephen J.; Mavropoulos, John C.; Wang, Amy; Darshan, Medha S.; Demark‐Wahnefried, Wendy; Pizzo, Salvatore V.; Aronson, William J.; Cohen, Pieter A.; Isaacs, William B.

doi:10.1016/s0022-5347(18)30410-5

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“…This diet forces the body to produce energy by ketolysis rather than by glycolysis (13,14). Recently, the efficacy of KD was proven slowing down tumor growth and increasing the survival of animals with malignant glioma (15), neuroblastoma (16), gastric cancer (17) and prostate cancer (18,19). The hypothesis is that normal cells could keep an efficient energetic metabolism, due to ketone bodies (lipid intake) and OXPHOS.…”

Section: Introductionmentioning

confidence: 99%

Ketogenic diet enhances the anti-cancer effects of PD-L1 blockade in renal cell carcinoma

Richard,

Beauvillain,

Benoit

et al. 2024

Front. Endocrinol.

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IntroductionClear cell renal cell carcinoma (ccRCC) is characterized by a predominant metabolic reprogramming triggering energy production by anaerobic glycolysis at the expense of oxydative phosphorylation. Ketogenic diet (KD), which consists of high fat and low carbohydrate intake, could bring required energy substrates to healthy cells while depriving tumor cells of glucose. Our objective was to evaluate the effect of KD on renal cancer cell tumor metabolism and growth proliferation.MethodsGrowth cell proliferation and mitochondrial metabolism of ACHN and Renca renal carcinoma cells were evaluated under ketone bodies (KB) exposure. In vivo studies were performed with mice (nude or Balb/c) receiving a xenograft of ACHN cells or Renca cells, respectively, and were then split into 2 feeding groups, fed either with standard diet or a 2:1 KD ad libitum. To test the effect of KD associated to immunotherapy, Balb/c mice were treated with anti-PDL1 mAb. Tumor growth was monitored.ResultsIn vitro, KB exposure was associated with a significant reduction of ACHN and Renca cell proliferation and viability, while increasing mitochondrial metabolism. In mice, KD was associated with tumor growth reduction and PDL-1 gene expression up-regulation. In Balb/c mice adjuvant KD was associated to a better response to anti-PDL-1 mAb treatment.ConclusionKB reduced the renal tumor cell growth proliferation and improved mitochondrial respiration and biogenesis. KD also slowed down tumor growth of ACHN and Renca in vivo. We observed that PDL-1 was significantly overexpressed in tumor in mice under KD. Response to anti-PDL-1 mAb was improved in mice under KD. Further studies are needed to confirm the therapeutic benefit of adjuvant KD combined with immunotherapy in patients with kidney cancer.

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Section: Introductionmentioning

confidence: 99%