Genetic and phenotypic plasticity of cancer

Team Leader : Charles Theillet

                            Claude Sardet

Institut de Recherche en
Cancérologie de Montpellier
Campus Val d’Aurelle
34298 Montpellier cedex 5

Tél. : 33 (0)4 67 61 37 66
Fax : 33 (0)4 67 61 30 41

Research topics

The Genetic and Phenotypic Plasticity of Cancer team is under the joint scientific leadership ofCharles Theillet and Claude Sardet who merged their teams in 2015. 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 are based on the exploration of the DNA safeguard pathway and the search for synthetic lethal interactions. Work is organized along three principal themes:


1: unravel the impact on resistance to treatment of breast and ovarian cancer of cell cycle checkpoint impairment. (more here)


2: Dissect the connections between the DNA safeguard pathways and mitochondrial and nucleotides metabolism to detect new leads of synthetic lethality. (more here)


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 stemness. (more here)


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Main Publications


Arnould S, Rodier G, Matar G, Vincent C, Pirot N, Delorme Y, Berthet C, Buscail Y, Noël JY, Lachambre S, Jarlier M, Bernex F, Delpech H, Vidalain PO, Janin YL, Theillet C, Sardet C. Checkpoint kinase 1 inhibition sensitises transformed cells to dihydroorotate dehydrogenase inhibition. Oncotarget. 2017 Jul 12. doi: 10.18632/oncotarget.19199. [Epub ahead of print]


da Silveira WA, Palma PVB, Sicchieri RD, Villacis RAR, Mandarano LRM, Oliveira TMG, Antonio HMR, Andrade JM, Muglia VF, Rogatto SR, Theillet C, du Manoir S, Tiezzi DG. Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype. Sci Rep. 2017 Jun 6;7(1):2851. doi: 10.1038/s41598 -017-02761-6.


Goguet-Rubio P, Seyran B, Gayte L, Bernex F, Sutter A, Delpech H, Linares LK, Riscal R, Repond C, Rodier G, Kirsh O, Touhami J, Noel J, Vincent C, Pirot N, Pavlovic G, Herault Y, Sitbon M, Pellerin L, Sardet C, Lacroix M, Le Cam L.E4F1-mediated control of pyruvate dehydrogenase activity is essential for skin homeostasis. Proc Natl Acad Sci U S A. 2016 Sep 27;113(39):11004-9. doi: 10.1073/pnas.1602751113. Epub 2016 Sep 12.


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. E4F1 controls a transcriptional program essential for pyruvate dehydrogenase activity. Proc Natl Acad Sci U S A. 2016 Sep 27;113(39):10998-1003. doi: 10.1073/pnas.1602754113. Epub 2016 Sep 12.


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