Jointly organized by the Embassy of France in Singapore, the Collège de France and the National Research Foundation, this lecture series forms part of the activities of the joint Committee for Science and Innovation France-Singapore.
French doctor and researcher, Professor Hughes de Thé is currently a hospital doctor and professor at the Collège de France, holder of the chair of cellular and molecular oncology (2014) and member of the French Academy of Sciences since 2011. His work, at the interface between biology and medicine, has radically transformed the management of a rare form of leukaemia, which has become the paradigm for targeted cancer treatments.
Our understanding of cancer has tremendously progressed in the past 30 years. The successive discovery of oncogenes, tumor suppressor genes, our understanding of signaling pathways, epigenetic regulations, immune interactions and the technological power of multi-omics have profoundly changed our vision of these devastating diseases. We are now faced with new challenges: the diversity of tumors, which emerge as a myriad of orphan diseases, and the integration of multiple layers of information (notably functional genomics) into prediction of tumor behavior and therapeutic sensitivity to conventional or innovative agents.
Our own empirical approach has been to leverage a simple, highly medically relevant, but rarely explored parameter: unexpected but unambiguous therapy response in patients. Exploration of the biological bases of therapy response in different models of cancer has led to some unexpected findings. Perhaps because we started from patient response, many of the therapeutic models derived from these studies ultimately proved highly relevant to patient care.
In the field of leukemia, will be presented the dissection of the basis for acute promyelocytic leukemia response to retinoic acid and arsenic. These converge onto mysterious nuclear domains, PML bodies, that enforce stress-induced senescence. Unexpectedly, the same pathway is implicated in MPN response to interferon, suggesting that it may represent a shared effector pathway of different anticancer therapies. Other studies suggesting that P53 inactivation can facilitate response to neoadjuvant chemotherapy will be presented and discussed.
These studies reconstructing therapy response have also unraveled novel important biological pathways (nuclear domains, proteolysis, stress response). Overall, tumors and tumor responses are a powerful source of inspiration for basic biology and academia-driven translational studies should be supported and facilitated.