Parent Category: Laboratoires Published: Friday, 17 February 2012

Genetic and phenotypic plasticity of cancer

SardetTheillet nouveau

 Claude SARDET and Charles THEILLET


 IRCM - U 1194

 208 avenue des Apothicaires, 34298 Montpellier


Phone: +33 4 67 61 25 84 (Sardet) or +33 4 67 61 37 66 (Theillet)

Mobile: +33 6 21 11 00 21 (Sardet)


Email :






The Genetic and Phenotypic Plasticity of Cancer team is located at the Montpellier Cancer Research Institute (IRCM U1194 and is under the joint scientific leadership of Claude Sardet and Charles Theillet who merged their teams in 2015. Claude Sardet is also the new director of the IRCM U1194 since 2015.
Our research is focused on resistance to treatment of breast and ovarian cancer and aims at overcoming it. Strategies to reach this goal and eradicate resistant tumor cells and cancer stem cells are based on the exploration of the DNA safeguard, signaling and metabolic pathways, and the search for synthetic lethal interactions. We address these questions on both cellular and animal models (including a very valuable collection /expertise on Human Primary Human tumor-derived xenograft models (PDTX)).
Work is organized along three principal themes:

1: Unravel the impact of cell cycle checkpoint impairment on resistance to treatment of breast and ovarian cancer.
2: Dissect the connections between the DNA safeguard pathways and mitochondrial, nucleotides and aminno-acids metabolism to detect new leads of synthetic lethality.
3: Identify the determinants of cancer stemness and determine their impact on phenotype plasticity and resistance to treatment. Explore the impact of our synthetic lethality approaches on this steaminess.


Keywords: cancer, cell cycle and repair checkpoints, transcription, cancer stem cells, metabolism, animal models for preclinical studies



Main publications

  • Arnould  S,  Rodier G, Matar G , Vincent C , Pirot N , Delorme Y ,  Berthet  C, Buscail Y , Noel  JY , Lachambre S , Jarlier M, Bernex F, Delpech H , VIdalain PO, Janin Y , Theillet  C, & Sardet C  (2017) Checkpoint kinase 1 inhibitor sensitises transformed cells to dihydroorotate dehydrogenase inhibition. Oncotarget. Jul 12;8(56):95206-95.
  • Kreuzinger C, Geroldinger A, Smeets D, Braicu EI, Sehouli J, Koller J, Wolf A, Darb-Esfahani S, Joehrens K, Vergote I, Vanderstichele A, Boeckx B, Lambrechts D, Gabra H, Wisman G, Trillsch F, Heinze G, Horvat R, Polterauer S, Berns E, Theillet C & Cacsire Castillo-Tong D. (2017 ) Molecular characterization of primary and recurrent high grade serous ovarian cancer. Clin Cancer Res  Dec 15;23(24):7621-7632.
  • Silveira W, Palma P, Sicchieri R, Villacis R, Mandarano L, Oliveira T,  Antonio H., Andrade  J, Muglia V,  Rogatto S, Theillet C*, du Manoir S. *, Tiezzi DG*. (2017)  Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype. Scientific Reports. Jun 6;7(1):2851.
  • Lacroix M*, Rodier G*, Kirsh O*, Houles T, Delpech H, Seyran B, Gayte L, Casas F, Pessemesse L, Heuillet M, Bellvert F, Portais JC, Berthet C, Bernex F, Brivet M, Boutron A, Le Cam L*, Sardet C* (2016) E4F1 controls a transcriptional program essential for pyruvate dehydrogenase activity. Proc Natl Acad Sci U S A. 2016 Sep 27;113(39):10998-1003.
  • Rodier G, Kirsh O, Baraibar M, Houlès T, Lacroix M, Delpech H, Hatchi E, Arnould S, Severac D, Dubois E, Caramel J, Julien E, Friguet B, Le Cam L, Sardet C. (2015) The Transcription Factor E4F1 Coordinates CHK1-Dependent Checkpoint and Mitochondrial Functions  Cell Reports.  Apr 14;11(2):220-33.
  • Colombo PE, du Manoir S, Orsett B, Bras-Gonçalves R, Lambros MB, MacKay A, Nguyen TT, Boissière F, Pourquier D, Bibeau F, Reis-Filho JS, Theillet C. (2015) Ovarian carcinoma patient derived xenografts reproduce their tumor of origin and preserve an oligoclonal structure,  Oncotarget.  Sep 29;6(29): 28327-40.
  • Du Manoir S, Orsetti B, Bras-Gonçalves R, Nguyen TT, Lasorsa L, Boissière F, Massemin B, Colombo PE, Bibeau , Jacot W, Theillet C. Breast tumor PDXs are genetically plastic and correspond to a subset of aggressive cancers prone to relapse. Mol Oncol. 2014 Mar;8(2):431-43.
  • Guedj M, Marisa L, de Reynies A, Orsetti B, Schiappa R, Bibeau F, MacGrogan G, Lerebours F, Finetti P, Longy M, Bertheau P, Bertrand F, Bonnet F, Martin AL, Feugeas JP, Bièche I, Lehmann-Che J, Lidereau R, Birnbaum D, Bertucci F, de Thé H, Theillet C. A refined molecular taxonomy of breast cancer. Oncogene. 2012 Mar 1;31(9):1196-206.
  • Paul C, Sardet C* and Fabbrizio E* (2012 ) The histone- and PRMT5-associated protein COPR5 is required for myogenic differentiation. Cell Death Differ. May;19(5):900 * Co-senior/corresponding author.
  • Hatchi E, Rodier G, Lacroix M, Caramel J, Jacquet C, Schrepfer E, Laguarrigue S, Linares L, Lledo G, Tondeur S, Dubus P, Sardet C* and Le Cam L* (2011) E4F1 deficiency results in oxidative stress-mediated cell death of leukemic cells. J. Exp. Med. Jul 4;208(7):1403-17.

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