Dynamics of chromatin states in breast cancer
6 December 2018 - 11 h 00
The dynamic nature of chromatin and transcriptional features are expected to participate to tumor evolution, particularly in the context of response to cancer treatment and acquisition of resistance. Yet, the contribution of epigenetic plasticity to cancer cells remains unclear and means to target it are still rather non-specific and inefficient, mostly due to the lack of relevant cellular models and in vivo datasets. We have recently achieved the mapping of histone marks at single-cell resolution in human breast tumors, enabling the investigation of the dynamics of chromatin marks, and its contribution to tumor evolution.
Using in vivo models of acquired resistance to cancer treatment, our recent data indicate that resistance to tamoxifen or chemotherapy may be associated with the emergence of an epigenetic subclone, characterized by a specific histone mark profile that could be stable along cell generations. More generally, the research projects of the group aim for a better understanding of the mechanisms of non-genetic selection, with the objective to design strategies to enhance or restore sensitivity to cancer treatments.