Childhood cancers: Providing new therapies more quickly

If today more than three-quarters of children and adolescents suffering from cancer are cured, it is thanks to the progress of research. Although it is well underway, the fight against cancer needs to step up. This is the aim of SIREDO, the center launched in November 2017, and which combines all of Institut Curie’s strengths - Treatment and basic, translational and clinical research - in the fight against cancer.

“Clinical research is vital to improve the recovery rate but also to reduce the after-effects of treatments,” explains Prof. François Doz, SIREDO’s deputy director of clinical research, innovation and teaching, and professor at Paris Descartes university. “SIREDO will help us to reduce the time lapse between the discovery of a new therapeutic lead and its application in a clinical setting.” This is the crux of the issue, and it will be achieved by bringing caregivers and scientists ever closer together.

Today’s research is tomorrow’s treatment

Great hope lies in better biological knowledge of the disease. The SIREDO teams are collaborating on a number of international studies. Only these will provide sufficient biological data on relatively rare tumors such as neuroblastoma and medulloblastoma, in order to establish a more precise prognosis and adjust treatments accordingly. These studies have already helped to limit treatments in some young patients suffering from diseases with a good prognosis: “therapeutic de-escalation” is a major breakthrough, given the side effects associated with cancer treatments.

“The search for biomarkers goes well beyond these prognosis data since biological data can also tell us which treatments to use,” adds the pediatrician. This is the aim of MAPPYACTS, coordinated by Gustave Roussy and for which Gudrun Schleiermacher - pediatrician and researcher - is joint investigator. Once their tumor has been sequenced to detect genome alterations, young patients whose therapies have failed are offered a targeted therapy, according to the tumor’s molecular profile.

And Prof. François Doz continues, “the latest progress in research points to the fact that the tumor cell is not the only source of information, and that the tumor’s microenvironment as well as circulating biomarkers - tumor cells, ctDNA, RNA, etc. from the tumor and which move around in the blood - can also be a source of information, with the enormous advantage of being detectable through a simple blood test.” Thus the MICCHADO study coordinated by Dr. Gudrun Schleiermacher, pediatrician and researcher at Institut Curie, is looking for circulating tumor DNA (ctDNA) in the blood or in other environments in young patients. By tracking these biomarkers and the immunological profile throughout patients’ treatment, the study hopes to better understand the mechanisms of the tumor’s growth and its resistance to treatment. Circulating biomarkers can thus be used for diagnosis, prognosis, risk prediction, therapeutic guidance and monitoring of the effectiveness of treatments.

Giving a boost to clinical research

Through its involvement for many years in basic and clinical research on this topic, Institut Curie has a number of assets to help transition from discovery to clinical application. If there’s an area that needs improvement it’s that of collaborations with industrial partners. Sandy Azzi-Hatem, manager of SIREDO and project manager in pediatric oncology explains: “SIREDO’s approach, an example of the research-care continuum, is a major asset for developing translational research and becoming a reference for harnessing and transferring technologies. We are in the process of developing partnerships with manufacturers for clinical and pre-clinical trials.”

“Although 200 young patients are already included in trials each year,” Prof. Doz reminds us, “we still need to expand them further in order to be able to offer our patients and their families the therapeutic innovations derived from the latest research breakthroughs, as quickly as possible.” And there are many of them, since in addition to the recent expansion of targeted therapies, immunotherapy is starting to demonstrate its effect in children and adolescents suffering from leukemia and in some cases, solid tumors. “Much progress remains to be made in this area,” admits the pediatrician, European coordinator of a trial to test the effectiveness of a new immunotherapy in the field of childhood brain tumors. “Because everything points to the fact that the immune mechanisms at play are different in children and in adults.” The SIREDO physician-researchers are already approaching the Cancer Immunotherapy Center at Institut Curie to clarify these mechanisms.

SIREDO provides a remarkable boost for research into childhood, adolescent and young-adult cancers. And as such it provides hope for patients and their families, as the mother of a child suffering from cancer and treated at Institut Curie reminds us: “We need research to move forward, quickly, very quickly. We know that it takes time to find and understand cancers, but when it affects us, our family, it becomes even more urgent. Research is hope.”