Hugues de Thé, is a French doctor and researcher. He is currently a hospital doctor and professor at the Collège de France, holder of the chair of cellular and molecular oncology, 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.
Thé's father was a doctor and biologist. He spent the first years of his life in the United States. After a period in preparatory classes, he studied medicine and biological sciences in parallel, first in Lyon, then at the Necker Hospital in Paris. Received at the Paris Hospital Boarding School in 1984, he chose the medical research internship he did in Pierre Tiollais' laboratory at the Pasteur Institute. His thesis and post-doctoral work in this laboratory will enable him to make significant contributions to the understanding of retinoic acid signalling, in particular with the cloning of RARB and the identification of the first element of response to this hormone. Together with Laurent Degos and Anne Dejean, he then explores the basis of the clinical response of acute promyelocytic leukaemias to retinoic acid, which will lead him to identify the reworking of the RARA gene in this disease and describe the PML/RARA fusion. Recruited as a researcher at Inserm in 1991, he devoted the rest of his career to understanding the leukemogenic function of this oncoprotein. After being recruited as a professor at the University of Paris 7 and hospital doctor, he was appointed head of a CNRSresearch unit, then CNRS/Inserm/University from 1995 to 2018. He is, or has been, a member of numerous evaluation and advisory structures in France and abroad. He is a member of the editorial boards of Cancer Research, then Cancer Discovery. His work, directly inspired by clinical observations and carried out in collaboration with French and Chinese teams, will lead to new insights into the roles of differentiation, gene expression control or nuclear organization in the pathogenesis of this disease. In particular, he will seek to understand the molecular and cellular bases of PML/RARA targeting by retinoic acid and later by arsenic. His team will demonstrate that retinoic acid and arsenic are targeted treatments that bind directly to PML/RARA and induce its degradation by the proteasome. In vivo modelling of the disease allows him to discover that the combination of retinoic acid and arsenic is capable of eradicating the disease. These models will find clinical application in treatments that can cure the vast majority of patients without the use of genotoxic chemotherapy. In addition to their medical applications, its work has opened up new perspectives in very fundamental biological fields, such as nuclear organization or protein stability control.
