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