Accelerating the pace of pediatric oncology research and innovating at Institut Curie, to better care for young patients

Examining the pediatric tumor microenvironment to develop new immunotherapies. Understanding the plasticity of cancerous cells to combat resistance to treatment. Identifying new methods for developing unique targeted therapies...
CP Septembre en or

Committed for almost 45 years to the fight against childhood cancer, the second most important cause of death in children under the age of 15, Institut Curie carries out cutting edge research, recognized internationally, in the diagnosis, treatment and care of children, adolescents and young adults with cancer.

Infographie 2021

Each year in France around 2,200 new pediatric cancer cases are diagnosed. Although over 80% of children are still living five years after diagnosis, it remains vital to develop new therapeutic strategies for those that cannot yet be cured, and to reduce the side-effects of traditional treatments.

At Institut Curie, between 300 and 400 young patients are treated every year by the multidisciplinary teams at the SIREDO center (Care, Innovation & Research in Childhood, Adolescent & Young-Adult Oncology). With the support of charity organizations, they conduct basic, translational and clinical research with a strong focus on solid tumors, including neuroblastoma, medulloblastoma, Ewing sarcoma, retinoblastoma and certain other brain tumors.

Dr. Olivier Delattre, Director of SIREDO and Research Director at Inserm: “Pediatric cancers are very different from adult cancers and thus require the development of specific research. At Institut Curie our strength lies in conducting multidisciplinary projects, as part of international collaborations that combine know-how in biology, physics, bioinformatics, genetics, clinical care and artificial intelligence with the most advanced genome sequencing and analysis technologies. As researchers and physicians, we work in synergy to refine the molecular profile of pediatric tumors, understand the mechanisms involved in the development of cancers, make the most accurate diagnoses possible and thus optimize treatments for our young patients.”

Understanding the biology of tumors to provide therapeutic innovations

Because decoding the most basic physio-pathological processes will provide the foundation for future treatments, Institut Curie’s researchers are using state-of-the-art technologies to analyze the confines of cells and of the genome. Internationally renowned, Institut Curie is a leading center for research and treatment of children and young adults suffering from Ewing sarcoma, a rare bone tumor that affects around 80 young patients each year in France. Dr. Olivier Delattre’s team recently highlighted the processes triggered by mutations that encourage formation of metastases in Ewing sarcomas.

In order to analyze in-depth the tumors that cause development of different types of medulloblastoma, tumors of the cerebellum that affect almost 130 children each year in France, the team headed by Olivier Ayrault, Research Director at the CNRS, head of the “Signaling in Development and Brain Tumors” team at Institut Curie, uses “multiomic” technologies (genomics, transcriptomics, proteomics). In 2018, using this approach, his team discovered the activation of a signaling pathway in the most common sub-group of medulloblastomas, paving the way for promising therapeutic options. “The extremely interesting aspect of basic research is that this pathway also seems to be activated in other pediatric cancers, providing a first step for strategies in several types of tumors and delivering great hope for future developments for our young patients,” explains Olivier Ayrault, European coordinator of the International Society of Pediatric Oncology (SIOP). “Currently I’m interacting daily with physicians to conduct large-scale projects involving other countries, and to move our discovery into clinical application.”

This work may change the future landscape for children, as did the discovery in 2008 by the team of Dr. Olivier Delattre and Isabelle Janoueix of a mutation involved in neuroblastoma (the third most common pediatric cancer), namely the mutation of the ALK gene. A current international study coordinated by Dr. Gudrun Schleiermacher, pediatric oncologist and Deputy Director of Translational Research at SIREDO, shows that alterations of the ALK gene are associated with a poor prognosis for high-risk neuroblastoma. This finding impacts treatment and is an argument in favor of including ALK inhibitors in the variables to be considered after diagnosis.

Molecular profiles of tumors: better diagnoses for better treatment

Mutations of the ALK gene, EWS-FLI1 translocation and NTRK fusion constitute research and technological breakthroughs that can be used to characterize hundreds of molecular signatures, particularly for pediatric tumors. These anomalies - which may be linked to genetic predispositions - help establish increasingly accurate diagnoses. The Somatic Genetics unit at Institut Curie, led by Olivier Delattre and Gaëlle Pierron, uses highly sophisticated new approaches to analyze close to 70 pathologies, over a hundred markers and treats close to 1,500 cases a year. These new molecular analysis methods are an integral part of clinical research.

New immunotherapies and therapeutic vaccines moving towards the clinical applications of the future

Immune cells have difficulty recognizing pediatric tumors, which explains the failure of immune checkpoint inhibitor treatments. However, immunotherapy is an emerging field of research in childhood cancers, and studies assessing strategies for boosting the immune system of young patients are multiplying.

This is the case of the IMMUNO-Ewing program, funded by the Ligue contre le cancer. This program aims to characterize specific targets of Ewing tumors in order to ultimately consider new immunotherapy approaches or therapeutic vaccination[1], including with RNA.

Although results from research laboratories sometimes lead to clinical trials, clinical observations also give rise to research projects. The proximity of the care and research teams at Institut Curie promotes synergies between basic, translational and clinical research. Within this context, Dr. Franck Bourdeaut, pediatrician and team leader at the Pediatric Oncology Translational Research laboratory (RTOP), is focusing in particular on rhabdoid tumors, which are rare but highly aggressive cancers affecting newborns and children in particular, and develop in a wide variety of organs, including kidney, liver and brain. In collaboration with the teams of Célio Pouponnot, Joshua Waterfall and Eliane Piaggio at Institut Curie, his project involves identifying the best immunotherapy targets in these rhabdoid tumors, and optimizing their treatments. Another aspect of the project involves assessing the combination of radiotherapy and immunotherapies for treating these rhabdoid tumors before future clinical trials can be considered.

The Proton Therapy Center at Institut Curie based in Orsay is the number 3 center worldwide in this field. This ultra-precise form of radiotherapy uses proton beams and is particularly suited to childhood tumors. The techniques are becoming more sophisticated and for a few years now Institut Curie has been the only center in France to treat the craniospinal axis in children using proton therapy.

[1] The principle of therapeutic (non-preventive) vaccinations against cancer is to encourage the immune system to attack the tumor cells. This involves the vaccine presenting the immune system with a tumor antigen (individualized, according to the molecular profile of the patient’s tumor) to trigger an effective immune reaction. With an RNA vaccine, an exogenous mRNA would lead to production of a tumor antigen protein and would cause an immune reaction that aims to destroy the cancerous cells.

Find out more

+ Link to the podcast “cancer in children and adolescents: an in-depth look at the pediatrics department”

+ Link to News COMPASS Project

+ Link to itw with Daniel Orbach on the PARTNER project 

+ (Re)view JICE 2021 Round table

+ The organizations alongside us