L'Institut de Recherche en Cancérologie de Montpellier :
«Ensemble, repoussons les limites»
CNRS UMR 9019 Paris-Saclay
Intégrité du génome et cancer
Gustave Roussy, Villejuif
contact : Eric JULIEN (Inserm/CNRS)
Replication stress resulting from slowing or stalling of DNA replication forks is a major driver of genome instability during cancer initiation and progression. DNA replication can be challenged as a consequence of oncogene activation or by agents that interfere with DNA synthesis, such as the ones used in chemotherapy. To accomplish genome duplication and prevent chromosomal instability, cells have evolved mechanisms that protect, stabilize and/or restart replication forks while delaying cell cycle progression, which avoids entering mitosis with under-replicated DNA. Over the last years, however, work from several laboratories including ours has shown that cells can progress into mitosis with under-replicated DNA. This led to the identification of mechanisms, mediated by the Fanconi anemia (FA) and Homologous Recombination (HR) repair pathways, that promote post-replication repair and rescue of under-replicated DNA in mitosis, allowing cells to divide and continue proliferating. I will discuss how these findings have advanced our understanding of the link between replication stress and genome instability; I will present a molecular pathway that connects mitochondrial stress and functions of FA proteins in genome maintenance; finally, I will show that mechanisms involved in mitotic rescue of under-replicated DNA may represent promising targets to selectively kill cancer cells that sustain intrinsically high levels of replication stress.
Division of Tumor Biology & Immunology, Oncode Institute.
Cancer Genomics Center Consortium
Netherlands Cancer Institute (NKI), Amsterdam
contact : Nathalie Bonnefoy (Inserm)
Leila Akkari, PhD is Assistant Professor and Junior Group Leader at the Netherlands Cancer Institute in Amsterdam. In 2019, she was nominated Junior Member of the Oncode Institute. After an MSc between Montpellier (France) and Manchester (UK), she performed her PhD studies in Cell Biology at the Institute of Molecular Genetics of Montpellier, CNRS - French National Research Center, France, and completed her postdoctoral training in cancer biology, immunology and genetics, first at the Memorial Sloan Kettering Cancer Center in New York City, USA, and then at the Ludwig Cancer Center in Lausanne, Switzerland. In 2017 she joined the Netherlands Cancer Institute in Amsterdam, where she established her research laboratory. Since early on in her scientific career, she has been interested in understanding the complex interactions between cancer cells and normal cells within tumors and she works towards elucidating how external signals regulate cancer malignancy. Research in her group focuses on the role of immune cells in tumor maintenance and therapeutic resistance in brain and liver cancer, in order to harness these cells in personalized anti-cancer treatments.She is recipient of prestigious personal research grants, such as the Vidi Research Grant from the Dutch Science Research Council (NWO) in 2020 and three research grants from the Dutch Cancer Society (KWF), including the Young Investigator Grant, Bas Mulder Award in 2017. In 2020, she was selected by the renowned life sciences organization European Molecular Biology Organization (EMBO) for their Young Investigator Program. In 2022, she is leading a multi-million euros consortium to target brain cancer with different immunotherapies and novel nanocarriers (NWO).
Centre d'Immunologie de Marseille-Luminy (CMIL), CNRS-INSERM, Université Aix-Marseille
contact : Laurent Le Cam (Inserm)
Centro de Investigación del Cáncer (CIC) and Instituto de Biología Molecular y Celular del Cáncer (IBMCC), CSIC-USAL, Salamanca, Spain
contact : Antonio Maraver (Inserm) -ATTENTION Séminaire décalé au vendredi 02 Juin à 14h
KRAS oncogenes have been identified in a quarter of all human lung tumors. Recently, several inhibitors were developed that target specific mutant KRAS isoforms and two of them, directed against the KRAS G12C oncoprotein, have just been approved. However, most patients develop resistance against these inhibitors and no actual survival benefits have been observed in clinical trials. Thus, it is urgently required to identify novel therapeutic options applicable to most if not all patients with KRAS-mutant tumors. I will discuss what we have learned from genetically engineered mouse models about the development of resistance to KRAS inhibition. Moreover, I will present novel insights into the mechanisms of KRAS signaling in lung cancer and how a better understanding of KRAS signaling may help to overcome resistance to targeting either KRAS itself or its MAPK effector pathway.
Centre de Recherche des Cordeliers, INSERM UMRS1138, Paris
contact : Florence Cammas (Inserm/CNRS)
«Ensemble, repoussons les limites»
«En à peine 20 ans, l'Institut de Recherche en Cancérologie de Montpellier (IRCM U1194) a su hisser sa recherche au meilleur niveau international dans le domaine de la cancérologie fondamentale et appliquée, recherche réalisée en étroite collaboration avec les services cliniques du Centre de Lutte Contre le Cancer de Montpellier (ICM: l’Institut du Cancer de Montpellier ), et des partenaires industriels. Sous la tutelle conjointe de l'Inserm, de l'ICM et de l'Université de Montpellier, l'IRCM rassemble aujourd'hui plus de 240 personnes, chercheurs, cliniciens, techniciens et étudiants, organisés en 16 équipes de recherche qui s'appuient sur des plateaux techniques performants et des services de soutien compétents. Dans un domaine de recherche extrêmement compétitif et en évolution toujours plus rapide, notre plus grand défi est de garder une longueur d’avance. Pour cela nous continuerons à structurer la recherche sur le cancer à Montpellier, à rechercher l’excellence et à accélérer l’innovation et le transfert au patient pour in fine contribuer à vaincre les innombrables formes différentes de cancer. Ensemble, repoussons les limites.»
Nathalie Bonnefoy, Directrice de l'IRCM