Cancer affects 35,000 young people every year in Europe, including approximately 2,500 in France. As the primary cause of death by disease in children and adolescents, it is responsible for 6,000 deaths annually across Europe, including 500 in France.
With its Crescendo medical-scientific programme dedicated to research into paediatric cancers, Gustave Roussy intends to step up the transformation of knowledge gained into therapeutic innovations, to shed light on the aetiology of childhood tumours, improve the cure of the latter and to predict long-term complications.
In recent years, major progress has been made in understanding the biology of childhood cancers. Gustave Roussy has taken the lead in integrating precision medicine into the care of young patients, generating molecular tumour information for each child and creating vast databases.
However, despite therapeutic breakthroughs in blood cancers with CAR-T cells, no new treatments have emerged for other cancers having a poor prognosis in children, especially brain tumours.
Gustave Roussy is developing the Crescendo programme as part of its 2020-2030 institutional strategic plan in response to this. Crescendo is a large-scale programme dedicated to childhood and adolescent cancers, led by Professor Gilles Vassal and Dr Dominique Valteau-Couanet, paediatric oncologists.
This programme brings medical teams and research scientists together to surpass the sequencing of paediatric tumours in a bid to speed up the transition period between acquiring knowledge and transforming it into therapeutic innovations. This will allow the teams to improve the quality of recovery of young patients and anticipate the sequelae. Crescendo is part of Gustave Roussy's major fundraising campaign "Curing childhood cancer in the 21st century".
The Crescendo programme seeks to make breakthroughs with scientific and societal impact in three areas:
- therapeutic innovations
- before cancer
- after cancer
The research scientists and doctors involved in the Crescendo programme are therefore channelling their research in two key directions in order to achieve the following objectives:
To deliver at least two solutions to change patient care
The Crescendo programme aims to deliver at least two products having a scientific and societal impact by 2025:
- a medicinal product: two projects have been launched and are currently in the pipeline to obtain a marketing authorisation (MA) for the treatment of childhood neuroblastoma: KIMOZOTM - an oral suspension, the research and development of which are being carried out by Gustave Roussy teams, and lorlatinib (LORVIQUATM) as part of an international trial sponsored by Gustave Roussy. Crescendo also aims to assess the medicinal product ONC201, which is looking promising for children presenting infiltrating brain stem gliomas, as part of the international BIOMEDE2.0 trial.
- an innovative care pathway: Gustave Roussy is also developing a holistic care and rehabilitation pathway in an attempt to assess and care for all children with cancer from a neuropsychological and psychosocial perspective. This is reflected in the generation of predictive scores for neurocognitive sequelae in children and adolescents receiving chemotherapy or radiotherapy and the implementation of appropriate rehabilitation modules for each child and his or her family, involving psychologists, neuropsychologists, school doctors, teachers, child psychiatrists, paediatric oncologists, speech therapists and psychomotor therapists.
To turn knowledge into therapeutic innovations
With this programme dedicated to childhood cancer, Gustave Roussy intends to speed up the transition period between gaining knowledge and transforming it into therapeutic innovations or management strategies. The aim is to allow as many young patients as possible to benefit from new treatments while ensuring optimum conditions for their recovery and anticipating long-term complications at the same time. To this end, clinicians and research scientists have joined forces to work on several research projects in different disciplines. The aim is to produce measurable progress in terms of survival or quality of life.
o The Immunology Project
With a few exceptions to the rule, effective immunotherapies in adult cancers have little positive impact on childhood cancers. A better understanding of the specific immunological features of childhood tumours is therefore needed. The aim of the immunology project is to investigate all of the interactions between the tumour and the child’s developing immune system. This will be achieved not only by developing immuno-organoids in order to reproduce in-vivo conditions as closely as possible, but also by exploring the role of the intestinal microbiota in children and adolescents in the body’s response to cancer. This project requires the collaboration of several research teams based at Gustave Roussy.
o The Genetics Project
This innovative project with a national dimension seeks to shed light on what causes cancer in children. The aim is to identify new cancer predisposition genes whilst honing in on the role of already known genetic abnormalities. This will be followed by an oncological risk assessment for each type of predisposition identified and the creation of national and international registries on which various research teams can rely in order to set up specific monitoring strategies in each case.
o The "multi-omics" integrated biology project *
This multi-omics integrated biology research project focuses on three types of cancer: a bone tumour, namely osteosarcoma, and two brain tumours, medulloblastoma and infiltrating brain stem glioma, for which no effective treatment exists. By increasing their knowledge of the mechanisms behind these cancers using data generated for each child and artificial intelligence, by identifying biomarkers associated with treatment response or disease recurrence and by analysing the tumour microenvironment, the teams of research scientists and clinicians involved are looking for therapeutic solutions to cure as many children as possible with these conditions.
o The Therapeutic Innovations project
In order to maximise the transformation of knowledge into novel treatments, the therapeutic innovations project of the Crescendo programme intends to use the Institute's databases to identify therapeutic targets, develop new medicinal products and evaluate them in phase I trials. By strengthening collaboration between the paediatric teams and its dedicated phase I department and linking with its industrial partners, Gustave Roussy hopes not only to increase the number of clinical trials and therapeutic innovations available to children and adolescents who have proved refractory to treatment, but also to develop new innovations in the field of precision medicine based on the knowledge acquired from the various projects in this programme.
o The After-Cancer Project
In order to improve understanding, screen for the disease and prevent late onset complications following treatment for childhood and adolescent cancers, Crescendo seeks to create a specialist paediatric post-cancer clinic as part of a wider programme of personalised cancer prevention highlighted in the Gustave Roussy Interception programme.
Gustave Roussy is also promoting clinical research into second cancers, cardiovascular and cerebrovascular complications as well as the long-term complications of new medicinal products such as targeted therapies and immunotherapies through the Interval programme.
* Multi-omics integrated biology: the use of multiple "-omics" technologies (genomics, proteomics, transcriptomics, epigenomics, metabolomics and microbiomics) to investigate life and biological phenomena in a focused, multidisciplinary manner.
