Genetic and phenotypic plasticity of cancer : Ch. Theillet/C. Sardet


The "Genetic and Phenotypic Plasticity of Cancer" team is led jointly by C Sardet (also Director of IRCM) and C Theillet, who merged their former labs at IGMM (C Sardet) and IRCM (C Theillet) in 2015. The new team, combines expertise on cellular metabolism, signaling, cell cycle checkpoints and transcriptional control (CS) and on breast and ovarian cancer genetics and cancer cell biology (CT). It has strong and long lasting ties with the clinics, illustrated by fruitful collaborations with Prof W Jacot, head of medical oncology and specialist of breast cancer, and Prof PE Colombo, oncosurgeon at ICM with a special interest in ovarian cancers, who have joined the team.

Projects are centered on Triple Negative Breast Cancer (TNBC) and High Grade Ovarian Cancer (HGOC), two aggressive female cancers, which respectively represent about 500 and 50 new patients treated at the ICM every year. Interestingly, despite their very different natural histories, both cancers share genetic characteristics such as the predominance of p53 mutations and the frequent inactivation of the BRCA pathway. For both cancers chemotherapy remains the sole therapeutic option and sustained remissions in advanced forms of the disease are rare. Therefore, the development of new treatment options is an urgent need. We aim at discovering novel Achilles’ heels for these aggressive cancers and build on them to explore novel therapeutic avenues based on synthetic lethality in order to eradicate the tumors along with cancer stem cells. Projects are built on our outstanding collection of 97 comprehensively characterized (omics, drug sensitivity) breast cancer and high grade ovarian carcinoma (HGOC) PDX models, as well as by a collection of genetically modified HMEC and TNBC cancer cell line models. The team is perfectly fluent in CSC biology and isolation of CSCs from both PDX and cancer cell lines


Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno N, Prat A, Chae Y, Lee K, Niikura N, Park Y, Xu B, Wang X, Gil-Gil M, Li W, Pierga J-Y, Im S-A, Moore H, Rugo H, Yerushalmi R, Zagouri F, Gombos A, Kim S-B, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron D Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690

du Manoir S, Delpech H, Orsetti B, Jacot W, Pirot N, Noel J, Colombo P-E, Sardet C, Theillet C In high-grade ovarian carcinoma, platinum-sensitive tumor recurrence and acquired-resistance derive from quiescent residual cancer cells that overexpress CRYAB, CEACAM6, and SOX2. J Pathol. 2022;257(3):367-378. doi:10.1002/path.5896

Jacot W, Heudel P-E, Fraisse J, Gourgou S, Guiu S, Dalenc F, Pistilli B, Campone M, Levy C, Debled M, Leheurteur M, Chaix M, Lefeuvre C, Goncalves A, Uwer L, Ferrero J-M, Eymard J-C, Petit T, Mouret-Reynier M-A, Courtinard C, Cottu P, Robain M, Mailliez A Real-life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program. Int. J. Cancer. May 14, 2019. doi:10.1002/ijc.32402

Fonti C, Saumet A, Abi-Khalil A, Orsetti B, Cleroux E, Bender A, Dumas M, Schmitt E, Colinge J, Jacot W, Weber M, Sardet C, du Manoir S, Theillet C Distinct oncogenes drive different genome and epigenome alterations in human mammary epithelial cells. Int. J. Cancer. 2019;145(5):1299-1311. doi:10.1002/ijc.32413

Idoux-Gillet Y, Nassour M, Lakis E, Bonini F, Theillet C, Savagner P Slug/Pcad pathway controls epithelial cell dynamics in mammary gland and breast carcinoma. Oncogene. 2018;37(5):578-588. doi:10.1038/onc.2017.355

Arnould S, Rodier G, Matar G, Vincent C, Pirot N, Delorme Y, Buscail Y, Noël J, Lachambre S, Jarlier M, Bernex F, Delpech H, Vidalain P, Janin Y, Theillet C, Sardet C Checkpoint kinase 1 inhibition sensitises transformed cells to dihydroorotate dehydrogenase inhibition. Oncotarget. 2017;8(56):95206-95222. doi:10.18632/oncotarget.19199

Lacroix M, Rodier G, Kirsh O, Delpech H, Seyran B, Gayte L, Casas F, Pessemesse L, Heuillet M, Bellvert F, Portais J-C, 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;113(39):10998-11003. doi:10.1073/pnas.1602754113

Rodier G, Kirsh O, Baraibar M, Houles T, Lacroix M, Delpech H, Hatchi E, Arnould S, Severac D, Dubois E, Caramel J, Julien E, Friguet B, Le Cam L, Sardet C The transcription factor E4F1 coordinates CHK1-dependent checkpoint and mitochondrial functions. Cell reports. 2015;11. doi:10.1016/j.celrep.2015.03.024

Colombo P, du Manoir S, Orsett B, Bras-Goncalves R, Lambros M, MacKay A, Nguyen T, Boissiere F, Pourquier D, Bibeau F, Reis-Filho J, Theillet C Ovarian carcinoma patient derived xenografts reproduce their tumor of origin and preserve an oligoclonal structure. Oncotarget. 2015;6. doi:10.18632/oncotarget.5069

du Manoir S, Orsetti B, Bras-Gonçalves R, Nguyen T-T, Lasorsa L, Boissière F, Massemin B, Colombo P-E, Bibeau F, Jacot W, Theillet C Breast tumor PDXs are genetically plastic and correspond to a subset of aggressive cancers prone to relapse. Mol Oncol. 2014;8(2):431-443. doi:10.1016/j.molonc.2013.11.010


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


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