Genetics and Metabolism of Rare Cancers
Director :
Judith Favier
Deputy Director :
Charlotte Lussey
Our main research interests are the genetics and biology of pheochromocytomas, paragangliomas (PPGL), and rare forms of kidney cancer. Strongly integrated into national and European research networks, the team consists of both basic and clinical researchers, working in synergy on multidisciplinary projects. We particularly focus on hereditary forms of PPGL caused by mutations in genes encoding the mitochondrial enzyme succinate dehydrogenase (SDH), which is involved in the tricarboxylic acid (TCA) cycle and the electron transport chain. Our research combines genetic, genomic, and epigenetic studies on patients, tumors, or liquid biopsies with experimental approaches that investigate the biology of these tumors in vitro or through preclinical studies. We aim to understand the links between deficient cellular metabolism, angiogenesis, epigenetic reprogramming, and carcinogenesis.
Scientific Themes
Metabolism and Biology
Dir: Judith Favier
This axis uses cellular and biochemical approaches to study oxidative stress-induced ferroptosis, the impact of SDHI fungicides and metabolic symbiosis with the microenvironment, and the effect of molecules secreted by SDH-deficient tumor cells (miRNAs, succinate) on the microenvironment.
Genetics and Genomics
Dir: Nelly Burnichon and Alexandre Buffet
The objectives are to perform the genetic characterization and toidentify somatic biomarkers for genomics-based precision medicine in paragangliomas, pheochromocytomas (PPGL) and rare forms of kidney cancer.
Preclinical and Clinical studies
Dir: Charlotte Lussey
Preclinical projects will aim to develop in vivo metabolic tracing approaches (fluxomics) to 13C-Glucose, and tumor metabolism imaging tools using magnetic resonance spectroscopy, with the objective of very rapid clinical transfer for the diagnosis and follow-up of patients with genetically determined forms of PPGL and RCC.
Main publications
Baudin E, Goichot B, Berruti A, Hadoux J, Moalla S, Laboureau S, Nölting S, de la Fouchardière C, Kienitz T, Deutschbein T, Zovato S, Amar L, Haissaguerre M, Timmers H, Niccoli P, Faggiano A, Angokai M, Lamartina L, Luca F, Cosentini D, Hahner S, Beuschlein F, Attard M, Texier M, Fassnacht M; ENDOCAN-COMETE; ENSAT Networks. Sunitinib for metastatic progressive phaeochromocytomas and paragangliomas: results from FIRSTMAPPP, an academic, multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial. Lancet. 2024;403(10431):1061-1070.
Amar L, Pacak K, Steichen O, Akker SA, Aylwin SJB, Baudin E, Buffet A, Burnichon N, Clifton-Bligh RJ, Dahia PLM, Fassnacht M, Grossman AB, Herman P, Hicks RJ, Januszewicz A, Jimenez C, Kunst HPM, Lewis D, Mannelli M, Naruse M, Robledo M, Taïeb D, Taylor DR, Timmers HJLM, Treglia G, Tufton N, Young WF, Lenders JWM, Gimenez-Roqueplo AP, Lussey-Lepoutre C. International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers. Nat Rev Endocrinol. 2021 Jul;17(7):435-444.
Goncalves J, Moog S, Morin A, Gentric G, Müller S, Morrell AP, Kluckova K, Stewart TJ, Andoniadou CL, Lussey-Lepoutre C, Bénit P, Thakker A, Vettore L, Roberts J, Rodriguez R, Mechta-Grigoriou F, Gimenez-Roqueplo AP, Letouzé E, Tennant DA, Favier J. Loss of SDHB Promotes Dysregulated Iron Homeostasis, Oxidative Stress, and Sensitivity to Ascorbate. Cancer Res. 2021 Jul 1;81(13):3480-3494.
Morin A, Goncalves J, Moog S, Castro-Vega LJ, Job S, Buffet A, Fontenille MJ, Woszczyk J, Gimenez-Roqueplo AP, Letouzé E, Favier J. TET-Mediated Hypermethylation Primes SDH-Deficient Cells for HIF2α-Driven Mesenchymal Transition. Cell Rep. 2020 Mar 31;30(13):4551-4566.e7.
Job S, Draskovic I, Burnichon N, Buffet A, Cros J, Lépine C, Venisse A, Robidel E, Verkarre V, Meatchi T, Sibony M, Amar L, Bertherat J, de Reyniès A, Londoño-Vallejo A, Favier J, Castro-Vega LJ, Gimenez-Roqueplo AP. Telomerase Activation and ATRX Mutations Are Independent Risk Factors for Metastatic Pheochromocytoma and Paraganglioma. Clin Cancer Res. 2019 Jan 15;25(2):760-770.
Buffet A, Morin A, Castro-Vega LJ, Habarou F,Lussey-Lepoutre C, Letouzé E, Lefebvre H, Guilhem I, Haissaguerre M, Raingeard I, Padilla-Girola M, Tran T, Tchara L, Bertherat J, Amar L, Ottolenghi C, Burnichon N, Gimenez-Roqueplo AP, Favier J. Germline Mutations in the Mitochondrial 2-Oxoglutarate/Malate Carrier SLC25A11 Gene Confer a Predisposition to Metastatic Paragangliomas. Cancer Res. 2018 Apr 15;78(8):1914-1922.
