Lectures

Oncology is the biological approach to the transformation of cells into cancer. First developed around 200 years ago, with morphological approaches, it has accelerated sharply in recent decades, with the discovery of the repertoire of genetic anomalies - most often acquired - that trigger disease. Numerous other branches of biology (epigenetics, immunology, cell biology, cellular interactions, etc.) have enriched the discipline. The first years of lectures at the Chair were devoted to the roles of viruses, the control of gene expression by " master genes " and the links between hormones and cancer. A new cycle is dedicated to a study of the mode of action of anti-cancer drugs.

Research

The common thread running through our research activities is the exploration of the cellular and molecular basis of the response to anti-cancer treatments, since only a detailed understanding of the mechanisms involved can lead to therapeutic optimization.

Our work concerns a rare form of leukemia, linked to a simple genetic anomaly and associated with extreme sensitivity to a hormone (retinoic acid) and a toxic agent (arsenic oxide). We have demonstrated that these two agents directly target the protein responsible for triggering this leukemia and induce its degradation by biochemical mechanisms that we have identified.

These studies led us to focus on sub-domains of the cell nucleus, the PML nuclear bodies, associated with the stress response and senescence, which are essential for a durable therapeutic response to this leukemia. The team has provided essential Spotlights on the formation and biochemical role of these domains. In particular, the team was able to demonstrate their essential role in the regulation of a post-translational modification, SUMO conjugation. PML facilitates sumoylation, but will also promote degradation of conjugated proteins via recruitment of STUbLs, a group of enzymes capable of recognizing SUMO and inducing ubiquitination.

More recently, we have been investigating the modes of action of other types of molecules, such as Actinomycin D and Doxorubicin. Unexpectedly, their activity is also modulated by the presence of Pml.