The laboratory “Genetics and Biology of Pediatric Tumors“ directed by Olivier Delattre at Institut Curie develop several research programs to understand the biology and oncogenic transformation mechanisms of various pediatric tumors and identify new therapeutic strategies that could improve patients outcome. Institut Curie provides an excellent scientific environment for high quality research with state-of-the-art equipments as well as a constellation of seminars covering many resarch areas. The successful postdoctoral applicant will join the neuroblastoma team on a translational research project funded by INCa/DGOS and led by Isabelle Janoueix-Lerosey in collaboration with a group at Gustave Roussy and one at CEA.
Research project Neuroblastoma is an embryonal cancer of the sympathetic nervous system that accounts for 8-10% of pediatric cancers. It represents an uttermost biological challenge for scientists and remains a disease with highly unmet medical needs for clinicians. The identification of ALK activating mutations has placed neuroblastoma among other ALKoma entities that may benefit from tumor-targeted therapies with tyrosine kinase inhibitors (TKIs) or monoclonal antibodies. The efficacy of new immunomodulatory antibodies, also called “immune checkpoint antibodies”, has been demonstrated in several aggressive adult cancers. Interestingly, it has been shown that various TKIs have not only cell-autonomous effects but also impacts on the immune microenvironment, providing a rationale for the use of TKIs in combination with immunomodulatory antibodies.
The whole project aims at exploring the link between ALK induced oncogenic stress and immune suppression within the neuroblastoma microenvironment, and then at evaluating the synergistic combination between therapies blocking these two hallmarks of cancer. The successful candidate will define the impact of ALK-driven oncogenic stress on the tumor immune microenvironment in our neuroblastoma mouse models. The candidate will also evaluate the therapeutic potential of a monoclonal ALK antagonist antibody alone or in combination with ALK TKIs in vitro and in vivo using various models. We expect to discover new insights into the biology of ALK-driven neuroblastoma, and provide the rationale for both tumor-targeted and immune-targeted therapies that may benefit to neuroblastoma patients.