Dynamics of repressive epigenomes in response to cancer treatments

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. 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 (Grosselin et al., Nat Genet 2019, Prompsy et al., Nat Comm 2020).  Using in vivo models of acquired resistance to cancer treatment, our data indicated 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 (Marsolier et al., biorxiv 2021).