CANSEARCH research platform in pediatric oncology and haematology of the University of Geneva
The research group works primarily in pediatrics in the areas of pharmacogenomics and individualized therapy, hematopoietic stem cell transplantation (HSCT), complications of treatment, and various types of childhood cancer. Its work is carried out in the following seven areas :
The various projects conducted in the field of pharmacogenomics consist of establishing, through various studies including numerous international collaborations, a link between the dose of chemotherapeutic drugs and response in children, with the aim of increasing their chances of survival and improving their quality of life by reducing the toxicity of the treatments. This new approach to individualized therapy makes it possible to identify biomarkers in order to better dose a drug while considering the genetics of the young patient. The research platform is responsible for several international studies in leukaemia, open in more than 20 countries (FORUM study, MyeChild study). The projects also aim to find markers of different toxicities, such as veno-occlusive disease or graft-versus-host disease, allowing better individualisation of a treatment before starting it. The group has received support from the Swiss National Science Foundation in these different areas. The BuGenes project, which stems from previous studies and concludes 15 years of work in the field of pharmacogenomics, consists of identifying biomarkers that can predict in advance the reaction of a child to treatment with Busulfan, the main agent used in the conditioning regimen prior to hematopoietic stem cell transplantation (HSCT). Its goal is to validate an algorithm to accurately and prospectively determine the dose of Busulfan to be administered to such a child, based on his or her genetics, for optimal therapeutic outcome. Indeed, reactions to this drug differ greatly from one child to another and individualization would increase its effectiveness.
HSCT, commonly known as bone marrow transplantation, involves injecting healthy stem cells back into the patient's body after the diseased stem cells have been destroyed during the pre-transplant conditioning regimen (based on chemotherapy). Conditioning is a very important time to make sure that the child is well prepared for the transplant, so that his or her body does not reject it (side effect). In addition to the translational research projects on HSCT already mentioned above, some clinical research projects on HSCT are also conducted in collaboration with the Paediatric Oncology and Haematology Unit of the HUG. As clinical research, the platform has an ongoing study under the direction of Dr. F. Bernard on HSCT in non-malignant diseases, in collaboration with the UK Paediatric BMT Group for HSCT in Fanconi anaemia. Similarly, two other studies are underway for the management of patients who should receive HSCT in general: a first with the EBMT Paediatric Disease Working Party on a predictive score for HSCT outcomes in paediatrics and a second in collaboration with French and English centres on the schooling of transplanted children.
The Paediatric Oncology and Haematology Scientific Research Platform is currently conducting a medical research project on paediatric liver cancer (hepatoblastoma and hepatocarcinoma), a very rare cancer, as it accounts for 1% of all childhood cancers. To carry out this project, Prof. Ansari has joined forces with other researchers from Europe, Japan and the USA, and has been a member of the Board of "CHIC" ("Children's Hepatic International Collaboration") for several years. The Children's Liver Tumour Group, integrated within the HUG, has national responsibility for all children with liver cancer, thanks to the international clinical study on the treatment of liver tumours in children, called "PHITT", a study of the SIOPEL group. This project has received the support of the European Union through the Horizon 2020 Programme, as well as support from the Swiss League Against Cancer. The next step of this project is to create an international registry of children with relapsed liver cancer (RELIVE), in order to improve the survival of children suffering from this pathology in the future.
The neuroblastoma oncogenetics project led by Dr. F. Gumy-Pause focuses on studying the efficacy of a molecule, PRIMA-1MET, recently discovered by our researchers as having the potential to act against neuroblastoma by reactivating a tumour suppressor gene (through the p53 protein). Neuroblastoma is an extracranial solid tumour that accounts for 8-10% of all paediatric cancers. Behind the term neuroblastoma there is a great diversity of tumours. 50% occur in children under 2 years of age. Among these, some can resolve spontaneously without any treatment. However, in other cases and in older children, the disease spreads to different organs (metastases) at the time of diagnosis, leading to an unfortunately sometimes fatal progression despite intensive chemotherapy. Based on the results obtained and already published by the platform in paediatric oncology and haematology, in-depth preclinical research is now necessary before moving on to clinical evaluation, which will provide essential data for new treatment strategies.
The paediatric neuro-oncology project led by Dr. A. von Büren is integrated into the clinical work of the University Hospitals of Geneva (HUG) and the research platform. Its aim is to enable, through a multidisciplinary approach, a better quality of care for children and adolescents suffering from brain tumours, the second most frequent cause of cancer in the paediatric age group. Initially, scientific research focuses mainly on high-grade gliomas (HGG) in children and adolescents, a disease with a prognosis that is often still extremely poor, with a survival rate of 20% after 3 years. This project aims in particular to create a register of data on these rare patients, in collaboration with working groups at European level, in order to better understand this disease and the disparities in diagnoses between young children (under 3 years old) and older children and adolescents.
The biobank project consists of the establishment of the 1st Swiss paediatric biobank (called BISKIDS), based in Geneva but with a national scope, aimed at storing the germline DNA of survivors of cancer diagnosed in paediatric age (about 7000 people to date). This national biobank will in fact be an evolution of the local biobank (called BaHOP, managed by Mr Denis Marino), already set up in 2016 by the research platform to collect biological material and clinical and demographic data from patients of the Paediatric Oncology Unit of the University Hospitals of Geneva (HUG). In addition to the local and national component, DNA samples are also collected abroad and stored in the biobank to carry out various studies. This infrastructure will eventually be accessible to any researcher in the field and will serve as a lever for discovery in the field of child cancer. To set up the national component of the biobank, the research platform is collaborating with the Childhood Cancer Registry in Bern. This collaboration also includes the project "BioLink - a contribution to the networking of biobanks for research purposes", which aims to link the Childhood Cancer Registry in Bern with the germline DNA biobank in Geneva. This BioLink project was awarded a grant from the Swiss National Science Foundation.
The GECCOS study ("Genetic risks for Complications in Children after Oncological treatment in Switzerland") aims to identify genetic markers in paediatric cancer survivors at risk of developing complications. Long-term clinical and epidemiological data on paediatric cancer survivors have already been collected nationally and have led to a large data set stored in the Childhood Cancer Registry in Bern. However, in these survivors, germline DNA (genetic data) has still to be collected and sequenced in order to associate genetic variants with the risk of complications, particularly in a genotype-phenotype association study. Thus, the workflow established for the collection and processing of germline DNA for this pilot study will also test the functioning and workflow of the biobank. The study will initially focus on the response and interaction between genes and lung toxicity (long-term respiratory complications), but also on ototoxicity (hearing impairment in adulthood) in cancer survivors in Switzerland. Various other toxicities, such as cardiotoxicity, can be analysed at a later stage.