On March 20 and 21, the French Society for the Fight Against Childhood and Adolescent Cancers and Leukemias (SFCE) held its first annual 2025 symposium in Paris. Over two days, numerous doctors and researchers presented their latest work. Among the notable advances, the conference highlighted new radiotherapy approaches to eradicate metastases, particularly intracerebral ones, discoveries in the biology of high-grade gliomas, and the development of CAR-T cells for the treatment of relapsed neuroblastoma.
For nearly 15 years, Imagine for Margo has supported these promising advancements. But these days were also an opportunity to present new research projects selected for their excellence as part of the latest call for projects. In 2025, Imagine for Margo is supporting 9 SFCE projects, with a total funding of €735,835. These projects will be funded thanks to donations collected through events such as the Children Without Cancer City Race, the Heart Rallies, and our continuous mobilization efforts.
3 projects exploring high-grade pediatric gliomas in depth
Since its inception, Imagine for Margo has strengthened researchers’ resources in the fight against childhood, adolescent, and young adult brain tumors, which are the leading cause of cancer-related deaths in children. Diffuse midline gliomas are the most common and severe form (with between 50 and 100 new cases each year in France). Unfortunately, these diseases have a very poor prognosis, with the vast majority of children passing away within two years of diagnosis. Until the BIOMEDE trial, attempts to improve patient survival with chemotherapy or targeted therapies had been unsuccessful. Thanks to the work of Dr. Jacques Grill, co-funded by Imagine for Margo, our knowledge of molecular alterations in gliomas has advanced significantly, particularly through comprehensive molecular profiling of tumors.
The data obtained have revealed mutations that can be targeted, finally enabling the development of effective precision medicine that can be combined with radiotherapy. This work has helped us understand why some children recover, leading to treatments being matched with specific molecular targets. Aware that this work must continue, we are pleased to support three projects that will provide even more detailed insights into the cellular and molecular complexity of brain gliomas.
Comprehensive profiling of high-grade pediatric gliomas: A first step toward new therapies
Dr. Claire Pacqueur (University of Nantes)
Imagine for Margo funding: €117,104
The diversity of high-grade gliomas and their ability to adapt to treatments make their management very complex. These tumors exhibit molecular and cellular states that can now be studied with advanced technologies. This project aims to explore these different states in-depth, as they coexist within high-grade pediatric gliomas. The study will be based on 20 cellular models and will use advanced molecular exploration techniques.
This exploration will:
- Understand and characterize the diversity of high-grade pediatric gliomas
- Identify treatment resistance mechanisms, including radiotherapy resistance
- Target tumor cells by finding specific ways to destroy cancer cells or prevent resistance development.
By gaining a clearer picture of the variability and evolution of high-grade pediatric gliomas, this research hopes to lead to more effective and personalized treatments, improving survival chances for children with this challenging cancer.
Molecular analysis of intercellular interaction networks in pediatric brain tumors
Dr. Florence Cavalli (Gustave Roussy, Paris), Dr. Franck Bourdeaut (Institut Curie, Paris), Dr. Arnaud Tauziede Espariat (St. Anne Hospital, Paris)
Imagine for Margo funding: €120,000
Pediatric embryonic brain tumors consist of four main entities: medulloblastomas (MB), atypical teratoid rhabdoid tumors (ATRT), embryonal tumors with multilayered rosettes (ETMR), and “other rare embryonal tumors.” This project focuses particularly on the rarest forms, notably central nervous system tumors with BCOR gene duplication.
Due to their rarity, these tumors are poorly studied, and our understanding of the processes responsible for their development is limited. They appear in very young children, with no standard treatment available, and unfortunately, the survival rate is low. The cellular heterogeneity of these tumors is one of the main causes of therapeutic failure, but it has not yet been studied at the molecular level. Researchers aim to identify and characterize the different types of cells that make up these tumors, as well as their spatial distributions. This project will help detect interactions between different types of tumor and non-tumor cells in contact, enabling better assessment of their role in tumor progression.
Study of a new target, VRK3, in high-grade pediatric gliomas
Dr. Marie-Anne Debily (Gustave Roussy, Paris) and Dr. Olivier Ayrault (Institut Curie, Paris)
Imagine for Margo funding: €117,900
Researchers in this project recently discovered that a new gene, VRK3, plays a crucial role in the development of midline gliomas. A reduction or loss of VRK3 leads to rapid and significant tumor cell growth impairment, making it a promising therapeutic target. However, no specific inhibitor for this protein currently exists. This study aims to develop a drug that specifically targets VRK3.
Using innovative analytical techniques such as proteomics and phosphoproteomics, the researchers will:
- Identify VRK3’s direct partners and those modified by it
- Determine the parts of VRK3 necessary for its activity
- Screen a library of 4 million compounds to identify those that could target these active regions
- Evaluate the best candidates for their ability to stop tumor growth in vitro.
Two projects to improve the cure and treatment of children and adolescents affected by neuroblastoma
A neuroblastoma is a malignant extracerebral tumor that develops from primitive nerve cells called neuroblasts, which form the peripheral nervous system. This type of solid tumor is one of the most common pediatric cancers (accounting for 1 in 10 cases). More than half of the children present with metastatic disease at the time of diagnosis. The exact causes of neuroblastoma remain unknown, and Imagine for Margo has funded numerous programs to better identify them: BEACON, RTOP, MICCHADO, and BIG DATA.
BEACON, led by Dr. Lucas Moreno (Hospital del Vall d’Hebron, Spain) and funded with more than €2 million by Imagine for Margo, has brought significant improvements in chemotherapy and immunotherapy treatments for relapsed patients, whose prognosis remains poor. We are also supporting promising programs, particularly those using artificial intelligence, such as DIGITWINS. This project, recently funded through FIGHT KIDS CANCER, aims to digitally replicate the most aggressive neuroblastomas by integrating all the molecular factors involved. This tool now enables better prediction of treatment efficacy and toxicity.
These advancements are important, but there is still much research to be done to better understand and anticipate relapses and to reduce treatment-related side effects for patients.
Identification of Prognostic and Predictive Circulating Biomarkers and Tumor Molecular Profiles in Children with Relapsed Neuroblastoma (BEACON Program)
Dr. Marion Gambart (Toulouse), Dr. Gudrun Schleirmacher (Institut Curie, Paris), Dr. Anne-Sophie Defachelles (Lille), Dr. Ludovic Manuy (Nancy), Dr. Carole Coze (Marseille), Dr. Estelle Thébaud (Nantes), Dr. Pablo Berlanga (Gustave Roussy), Dr. Benoit Dumont (Centre Léon Bérard, Lyon), Dr. Julie Tandonnet (Bordeaux), Dr. Hélène Boutroux (Trousseau, Paris), Dr. Sarah Jannier (Strasbourg).
Funding from Imagine for Margo: €59,131
Today, thanks to the BEACON trial, children benefit from an innovative therapeutic combination, where chemotherapy is combined with immunotherapy. While progress has been significant, too many children still succumb to disease relapse. To better understand disease progression, treatment efficacy, and to improve relapse prediction, it is essential to deepen this clinical research project with so-called “exploratory” studies.
As part of this project, researchers will thoroughly characterize neuroblastoma tumor cells by analyzing genes (circulating DNA and messenger RNA) in all children participating in BEACON 2. Blood and bone marrow samples will be taken before treatment begins and at the start of each therapeutic cycle (12 in total, except in cases of progressive disease or unacceptable toxicity).
Study on the Neuropsychological Impact of Lorlatinib in High-Risk Neuroblastoma Patients
Dr. Claudia Pasqualini (Gustave Roussy), Dr. Zoé Barrault (Gustave Roussy), Dr. Pablo Berlanga (Gustave Roussy)
Funding from Imagine for Margo: €98,700
Alteration of the ALK gene is associated with a poor prognosis in neuroblastoma patients. Recent clinical trials have shown that Lorlatinib, a drug specifically targeting this gene, improves survival in patients with this alteration. However, this drug can cause significant side effects, particularly on the central nervous system. More than 10% of treated adult patients have experienced symptoms ranging from mood swings to severe cognitive impairments.
This project aims to conduct in-depth neuropsychological assessments of children treated with Lorlatinib to better understand its cognitive and neurological consequences. These analyses will help physicians optimize symptom management and, in the long term, improve the quality of life of children with high-risk neuroblastoma.
Continuing the Fight Against Ewing Sarcoma in Children : The REGO-INTER-EWING 1 Trial
Ewing sarcoma is the second most common malignant bone tumor in adolescents and young adults, after osteosarcoma. In France, approximately 80 to 100 new patients are diagnosed each year. The majority of cases (70%) occur in individuals aged 5 to 25, although these tumors can also be diagnosed before the age of 5 and after 30. Most Ewing sarcomas develop in bones, but 15% can arise in soft tissues outside the bones. Unfortunately, metastases are detected at diagnosis in one-third of patients. Of these metastases, 50% are located solely in the lungs, while others spread to different bones or the bone marrow. Other severity factors include tumor location, size, and response to treatment.
In 2021, the FIGHT KIDS CANCER consortium selected the REGO-INTER-EWING 1 project for its scientific excellence and its significant impact on unmet medical needs. This multinational clinical research project aims to improve the prognosis of children diagnosed with metastatic Ewing sarcoma. The clinical team is testing a new chemotherapy protocol combined with regorafenib in 24 children. This molecule is particularly promising as it targets multiple proteins from the same family that are heavily involved in the disease.
INTER-EWING-1: A Clinical Study on the Combination of Regorafenib with Conventional Chemotherapy for the Treatment of Patients Diagnosed with Metastatic Ewing Sarcoma
Dr. Pablo Berlanga (Gustave Roussy, Paris), Dr. Nathalie Gaspar (Gustave Roussy, Paris), Dr. Marta Jimenez (Unicancer, Paris)
Funding from Imagine for Margo: €60,000
This funding supports a crucial step in the REGO-INTER-EWING 1 clinical trial: randomization, which involves creating two cohorts (standard treatment vs. standard treatment + regorafenib). This is the only way to scientifically demonstrate the therapeutic benefit of regorafenib.
This important clinical work is part of Imagine for Margo’s broader commitment to defeating this devastating cancer. For example, we have supported the research of Dr. Olivier Delattre (Institut Curie) and Dr. Sophie Postel-Vinay, who won the first Innovation Award from FIGHT KIDS CANCER. In 2022, this consortium also selected the NEWTARGETS project, which aims to target abnormal proteins specifically produced in Ewing sarcoma that are essential for cancer cell proliferation. The researchers will develop targeted immunotherapy strategies against these abnormal proteins.
Continuing to Innovate to Defeat Acute Myeloid Leukemia in Children and Adolescents
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. AML is the second most common leukemia in children, after acute lymphoblastic leukemia. Each year, approximately 80 children in France are diagnosed with AML. This type of leukemia is most frequently observed during the first two years of life and adolescence. Although more than 90% of children achieve complete remission, the relapse rate remains high (40 to 50%), despite advances in understanding tumor mechanisms, risk group stratification, and improvements in intensive chemotherapy and bone marrow transplantation. The overall risk of relapse remains the most common cause of death.
Strengthening T Lymphocytes to Prevent AML Relapse
Dr. Fanny Alby-Laurent (Armand Trousseau, Paris) and Dr. Yannick Simoni (Institut Cochin, Paris)
Imagine for Margo funding: €25,000
To reduce the risk of relapse and the need for bone marrow transplants, which remain highly toxic for patients, new therapeutic strategies must be explored. As seen in patients with solid tumors (melanomas, digestive cancers, etc.), the idea of mRNA vaccination is gaining traction in pediatric oncology, particularly to immunize patients against AML cancer cells. The goal of this project is to make vaccination effective by identifying the specific proteins produced by tumor cells. This preliminary work is essential to develop an mRNA vaccine that effectively strengthens the immune system against residual leukemic cells, which are responsible for relapse.
To combat this devastating disease, Imagine for Margo has also funded projects for early relapse detection through genetic analysis (SFCE 2024 project, PG-AML) and the large-scale ALARM3 study. ALARM3 is part of a major French program, CONECT-AML, dedicated to investigating the molecular mechanisms involved in relapsed AML and utilizes a wide range of study models, including cultured cells and comprehensive genetic analyses of patient samples.
Sustaining Pediatric Oncology Databases to Advance Research
Databases play a crucial role in pediatric oncology research and care, providing a better understanding of childhood cancers and optimizing treatments. They centralize valuable information on tumor characteristics, administered treatments, and patient responses, facilitating the identification of new therapeutic strategies. In research, they help detect molecular factors, refine clinical trials, and accelerate innovation through large-scale analyses. In clinical care, they enable more personalized medicine by providing doctors with data and results that help tailor treatments or securely grant access to innovative therapies (e.g., SACHA).
Recognizing their importance in research and care, Imagine for Margo has decided to fund the continuation of two databases for the next two years.
FRACTURE 2 : The French Database for Very Rare Pediatric Tumors
Dr. Yves Réguerre (La Réunion), Dr. Coralie Machebranche (Angers), and Dr. Daniel Orbach (Institut Curie, Paris)
Imagine for Margo funding : €18,000
Nearly 10% of cancers diagnosed in children and adolescents are “very rare tumors,” affecting fewer than two children per million. Due to their rarity, these tumors are the subject of only a few studies, making it difficult to establish treatment recommendations. Since 2012, the database of the Committee for Very Rare Pediatric Tumors (FRACTURE), affiliated with the French Society for the Fight Against Childhood Cancer and Leukemia (SFCE), has enabled the national registration of these very rare tumors in children and adolescents. As of January 1, 2024, 784 patients have been registered, covering 129 different diagnoses. This data has contributed to numerous national and international studies. Given the small number of patients affected by each condition in each country, it is essential to collaborate and share data and expertise at a European level. With this funding, the team aims to improve data quality within the FRACTURE database by creating more specific records for each tumor type and harmonizing data collection with other European groups to participate in an international registry in the future.
PREDCAP – National Observatory of Cancer Predisposition Genes in Children and Adolescents
Dr. Léa Guerrini-Rousseau (Gustave Roussy, Paris), Dr. Franck Bourdeaut (Institut Curie, Paris), Dr. Claire Bougeard (Rouen), Dr. Nadège Corradini (Centre Léon Bérard, Lyon), Dr. Florent De Vathaire (Gustave Roussy, Paris)
Imagine for Margo funding: €120,000
The National Observatory for Genetic Cancer Predisposition Syndromes in Children (PREDCAP) aims to enhance our understanding of pediatric cancer predisposition syndromes to optimize patient and family care. Recent studies report that a mutation in a major cancer predisposition gene is identified in 7 to 8% of children diagnosed with cancer. More than 60 cancer predisposition syndromes have been identified, and this number is rapidly increasing with advancements in genetic analysis. One of the key challenges for physicians is recognizing these genetic predispositions, adapting treatment and monitoring accordingly, and offering appropriate genetic counseling to families.
PREDCAP is a unique tool in France, available in all SFCE pediatric oncology centers, with the following objectives:
- Collecting and structuring information (medical, genetic, and familial data) on childhood cancers associated with cancer predisposition syndromes.
- Creating a virtual biobank (information on available biological samples).
- Providing access to this information after scientific committee approval.
Active since 2021, PREDCAP is operational in 20 SFCE centers and has already included 221 patients. Imagine for Margo’s funding will allow this project to continue by expanding center participation, increasing patient records, maintaining personnel, and covering data hosting server costs, with the ultimate goal of ensuring PREDCAP’s long-term sustainability.
Supporting Imagine for Margo to Defeat Childhood Cancer
Significant advancements in pediatric oncology have emerged in recent years thanks to the projects we fund, made possible by the growing support for our association each year. At Imagine for Margo, we firmly believe that uniting efforts, breaking down silos, and fostering collaboration will one day lead to the eradication of pediatric cancers. Together, we are stronger! Join us in providing hope for recovery to every child, adolescent, and young adult.
GO, FIGHT, WIN!
