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    Pierre Bigot

    Pierre Bigot

    University Professor-Hospital Practitioner

    pierre.bigot@univ-angers.fr

    Keywords: Renal cell carcinoma, Ketogenic diet, Immunotherapy

     

     

     

     

    State of the art and objectives

    In 1924, O. WARBURG has described the cancer as a metabolic disease. He described a « metabolic switch » in the tumor characterized by an energy production from the glucose (aerobic glycolysis) and no longer by the mitochondrial oxidative phophorylation. A ketogenic diet forces the body to burn fat instead of glucose. Fat metabolism occurs via the mitochondial oxidative phosphorylation. The ketogenic diet showed a benefit in drug resistant epilepsy and childhood metabolic disorders such as GLUT-1 deficiency. Recently, it has been introduced as an adjuvant therapy for glioma patients. Several studies have confirmed the presence of a metabolic change in renal cell carcinoma. Analysis of data from the TCGA database has also described in renal cell carcinoma, an overexpression of genes involved in aerobic glycolysis and an overexpression of genes involved in oxidative phosphorylation. 10 % to 40 % of patients are newly diagnosed as metastatic and 10 % to 30 % will become metastatic. Recently, NIVOLUMAB plus IPILIMUMAB showed a significant overall survival benefit over SUNITINIB as the first line treatment for intermediate and high-risk patients with metastatic renal cell carcinoma. Our objective is to evaluate the efficacy of a ketogenic diet, enriched with medium chain triglycerids, and NIVOLUMAB plus IPILIMUMAB in metastatic renal cell carcinoma.

     

    Main results from the last 5 years

    Our preclinical data showed that ketogenic diet can slow ccRCC tumor growth in a mouse model. Tumors analysis after ketogenic diet identified a modification of the tumor metabolism and immunity with an overexpression of PDL1 . We think that ketogenic diet has a direct effect on tumor growth and could potentiate the effect of the immunotherapy treatment used in renal cell carcinoma.

    People involved

    • Pierre Bigot (MD, PhD)
    • Vincent Procaccio (MD, PhD)
    • Magalie Barth (MD)
    • Maxime Benoit (MD)
    • Cyrielle Rolley (PhD student)
    • Jeremy Richard (PhD student)
    • Cecile Aubert (MD student)

     

    Main publications and patents from the 5 last years.

    • Bigot P, Colli LM, Machiela MJ, et al. Functional characterization of the 12p11.23 renal cancer susceptibility locus implicates BHLHE41. Nature Commun. 2016 Jul 7;7:12098 
    •  Scelo G, Hofmann JN, Banks RE, Bigot P, Bhatt RS, Cancel-Tassin G, Chew SK, Creighton CJ, Cussenot O, Davis IJ, Escudier B, Frayling TM, Häggström C, Hildebrandt MA, Holcatova I, Johansson M, Linehan WM, McDermott DF, Nathanson KL, Ogawa S, Perlman EJ, Purdue MP, Stattin P, Swanton C, Vasudev NS, Wu X, Znaor A, Brennan P, Chanock SJ. International cancer seminars: a focus on kidney cancer. Ann Oncol. 2016 Aug;27(8):1382-5
    • Cornu JN, Cancel-Tassin G, Cox DG, Roupret M, Koutlidis N, Bigot P, Valeri A, Ondet V, Gaffory C, Fournier G, Azzouzi AR, Cormier L, Cussenot O. Impact of Body Mass Index, Age, Prostate Volume, and Genetic Polymorphisms on Prostate-specific Antigen Levels in a Control Population. Eur Urol. 2016 Jul;70(1):6-8
    • Lebdai S, Verhoest G, Parikh H, Jacquet SF, Bensalah K, Chautard D, RiouxLeclercq N, Azzouzi AR, Bigot P. Identification and validation of TGFBI as a promising prognosis marker of clear cell renal cell carcinoma. Urol Oncol. 2015 Feb;33(2):69.e11-8
    • Baize N, Bigot P. Immunotherapy in renal cell carcinoma: A booming clinical research. Prog Urol. 2018

     

    Main Collaborations:

    • Department of Urology, Angers University Hospital
    • Department of Epidemiogenetic, National Cancer Institute, USA
    • URoCCR network

               

    Acknowledgements for the financial supports

    • Ligue contre le cancer
    • CHU Angers
    • National Cancer Institute
    • Région des Pays de la Loire
    • Association Française d’Urologie