Better diagnoses, new treatments… all the research carried out by Olivier Delattre has a clinical application. Nothing is left to chance. A researcher for the past 25 years, he has never lost sight of the fact that he is also a trained pediatrician.
Director of the Cancer genetics and biology unit at the Institut Curie in Paris, Olivier Delattre has just been awarded the 44th Léopold Griffuel cancer research prize by the Fondation ARC. At the awards ceremony, the Foundation indicated: "At the interface of fundamental and translational research, his work has a direct impact on clinical research." A few words that perfectly sum up the career of this childhood cancer expert, who has worked in research for 25 years while remaining true to his background as a pediatrician.
It all began for him with a degree in medicine.
It was almost by chance that I ended up doing my first medical internship in pediatrics, but I quickly got a taste for it. So in 1982, I set off for an international cooperative placement in Dakar, Senegal. This gave me an amazing breadth of clinical experience”, he recounts. “When I got back to France, I shifted my focus to hematology, the study of blood diseases. But research appealed to me because I really wanted to understand how scientific and then medical knowledge emerged in the lab
To satisfy his curiosity, he suspended his medical internship to spend a year in the tumor genetics lab founded by Gilles Thomas at the Institut Curie. This was a deliberate choice. "At the time, the discoveries made at the end of 1970s relating to the oncogenes responsible for cancers in animals were finding their first applications in humans. It was very exciting”, he recalls. “In addition, as an École Polytechnique graduate, physician and biologist, Gilles Thomas had a brilliant mind and encyclopedic knowledge. He was my first mentor." The following year, he continued his research work as part of the team led by Richard Breathnach at the laboratory for the molecular genetics of eukaryotes directed by Pierre Chambon in Strasbourg.
"Both these experiences had a huge impact me, with a more functional approach to genetics", he explains. Then, after a few months at Massachusetts General Hospital in Boston, USA, he returned to Gilles Thomas’ lab and resumed his pediatric oncology internship. "It emerged that Jean-Michel Zucker, head of the pediatric department at the Institut Curie, encouraged his students to train in research. He was a true visionary, convinced that this approach was crucial to the quality of clinical and fundamental research”, stresses Olivier Delattre, who took little persuasion. “For two slightly tricky years, I was a medical intern by day and a researcher by night."
Once he had obtained his two doctorates - one in medicine and the other in the molecular biology of eukaryote organisms - it was impossible to continue at the same hectic pace. Recruited by Inserm, he opted for research, but he did not forget his young patients, focusing his studies on pediatric oncology. "The study of tumors in children is made slightly easier by the fact that they are genetically stable, with practically no environmental influence”, he specifies. “To a certain extent, they serve as simplified models, the mechanisms of which can also be found in adult tumors.” A dual observation that proved to be true. A few months after he opted to stay with Gilles Thomas’ team, the latter identified and characterized the genes altered by chromosome translocation - i.e. by swapping genetic material between two chromosomes – causing Ewing’s sarcoma, a type of bone cancer in children and young adults. Since this world first, his team has shown that the EWS- FLI protein (standing for Ewing Sarcoma - Friend Leukemia Integration) resulting from this modification regulates several signaling pathways involved in abnormal cell proliferation, "especially the IGF1 (Insulin-Like Growth Factor-1) pathway, a growth factor for which inhibition has been shown to be effective in a phase I clinical trial” [editor’s note: conducted by Pfizer], he indicates.
Furthermore, this research led to better diagnosis as well as the characterization of a new family of cancers, rhabdoid tumors, so called because they share common traits with rhabdomyosarcomas, childhood muscle tumors. These tumors primarily affect the kidneys and the central nervous system, but they can also develop anywhere in the body. "They have been shown to be heterogeneous and some forms resemble Ewing’s sarcoma. However, we have demonstrated that they are actually a completely different family, characterized by inactivation of a tumor-suppressor gene, Smarcb1, involved in a protein complex responsible for remodeling chromatin, the condensed form of DNA in the nucleus of our cells", explains the researcher. Once again, this work has resulted in better diagnosis and the development of a treatment. Tazemetostat, developed by EpiZyme, is currently the subject of an international clinical trial that the Institut Curie is participating in. In addition, "it has been shown that abnormalities in this complex have been observed in almost 20% of adult cancers", adds Olivier Delattre.
Finally, "initially at the request of clinicians, we turned our attention to neuroblastoma, an extracranial solid malignant tumor that affects young children. The behavior of this tumor is really fascinating: in some cases, it regresses all by itself, while in others it is very aggressive and resistant to treatments”, explains the researcher. We have shown that these tumors are associated with abnormalities in the gene encoding the ALK (anaplastic lymphoma kinase) membrane receptor." Briefly, when this receptor is mutated, it functions permanently in the tumor nerve cells causing them to proliferate, whereas this proliferation is stopped when it is blocked. Once again, a clinical trial is under way in France with crizotinib, a treatment that inhibits ALK. Today, the Fondation ARC prize allows Olivier Delattre to reinforce his team, which espouses his own approach, at the crossroads of fundamental and clinical research. This is reflected by the fact that, "within the unit directed by myself, one team is led by two pediatricians who, like me, completed a scientific Ph.D. thesis”, he explains, delighted to have inspired others to follow his example.
And he has no shortage of examples to persuade them.
Working on cancer is absolutely fascinating”, he says. “For doctors, it means finding the disease’s Achilles heel, so they can treat patients more effectively. For researchers, it means studying a very strange biological object; almost universal within the animal kingdom, the origin and potential role of which in the evolutionary process remain very unclear.
Find out more about Olivier Delattre
Olivier Delattre directs the Cancer genetics and biology unit (Inserm unit 830/Institut Curie – Paris-Descartes University) at the Institut Curie in Paris.
- 1981 Paris Hospitals intern
- 1990 Doctor of medicine
- 1991 Doctor of molecular biology of eukaryote organisms
- 1988-1998 Researcher at the Tumor genetics unit, Institut Curie
- Since 2007 Director of the Cancer genetics and biology unit, Institut Curie
- Since 2012 Director of the Site de recherche intégré sur le cancer (Siric - integrated cancer research site) at the Institut Curie