In 2020, the first call led to the selection of six innovative projects for a total amount of 3,08 million euros. These 6 projects are about the following diseases: high-grade gliomas (2 projects), acute myeloid leukaemia, rhabdoid tumours, osteosarcoma and neuroblastomas.
AsiDNA clinical trial on high-grade gliomas
High-grade glioma (HGG) is one of the most common malignant childhood tumours of the central nervous system (brain tumour).Standard treatment for HGG consists of surgery when possible and radiotherapy in all cases.
Chemotherapy or other drugs in clinical trials may be added during and/or after radiotherapy depending on HGG subtype. In most cases, after this first-line treatment, the cancer comes back – in some subtypes, 100% children relapse.
This is why this study, called “AsiDNA Children”, is trying a new drug: AsiDNA.
The hypothesis of the “AsiDNA Children” study is that, in children and adolescents with recurrent previously irradiated HGG, this drug
in association with radiotherapy will prolong survival and improve patients’ quality of life.
It will be given in association with radiotherapy in children and adolescents with recurrent HGG that have previously been treated with radiotherapy, which is a situation where there
is no known curative treatment today.
AsiDNA is a new kind of drug that could be effective to treat HGG because its mechanism of action increases the vulnerability of tumour cells to radiotherapy without attacking other healthy parts of the body.Financed: 580 000 €Duration: 1 yearCountries: France, Italy, Netherlands and GermanyDisease: High grade gliomaStatus: Ongoing
POBCORN program on brain tumors
Researchers recently identified a new subtype of central nervous system tumour: the high-grade neuroepithelial tumour with a BCOR-alteration (CNS HGNET-BCOR). This tumour has distinct molecular characteristics, is highly aggressive and has a poor clinical prognosis.To date we do not know which biological processes drive this tumour type and no effective treatments exist.
The collaborative project POBCORN aims at in-depth investigation of CNS HGNET-BCOR biology with cutting-edge molecular technologies.A “multi-omics” approach will be used improve our understanding of this tumour type at several levels:- Patients’ stratification (or classification), and
– Identification of novel treatment approaches (on the basis of this novel stratification).The “omics” consist of various analysis tools (molecular biology, radiography…) that enable a better characterisation and understanding of diseases or the functioning of our body.
In this case, multi-omics approach means that tumour tissue will be analysed with several techniques and different angles, such as:
– Genomics (gene transcription)
– Epigenomics (epigenetic analysis -see EpiRT project for explanation on this)
– Transcriptomics (transcript analysis of the gene or how each gene transcription leads to the creation of proteins)
Once this newly identified tumour type is better characterised, the study will test in a pre-clinical setting several identified drugs which show potential promises to improve the treatment for those children with a poor prognosis.
In summary, the objective of the POBCORN project is to identify which events lead to tumour growth as well as potential therapeutic targets.
It also aims at providing first translational guidance on how to treat CNS HGNET-BCOR patients in future clinical trials. The BCOR alteration is mostly found in central nervous system tumours such as glioblastoma, medulloblastoma, ependymoma but also in clear cell sarcoma, acute myeloid leukaemia and retinoblastoma. In the longer run, those findings will also benefit those latter patients.Financed: 498 000 €Duration: 2 yearsCountries: Austria and GermanyDisease: Brain tumoursStatus: Ongoing
ALARM 3 program on acute myeloid leukemia
Many children with acute myeloid leukaemia’s (AML) relapse (35-45%) and the overall survival chances remain low (60-75%).
Genetic abnormalities carried by AML cells are responsible for the relapse and the occurrence of the mechanisms of resistance to treatment.We now know that the cells from the microenvironment of the bone marrow play a role in “maintaining” AML cells and in mechanisms of resistance to treatment. This project “ALARM3” will focus on AML cells at relapse and the understanding of their interactions with the bone marrow microenvironment in order to develop new treatments.The project team will work in close collaboration with French and British teams that carry out a clinical trial for children with relapsed or refractory acute myeloid leukaemia.This project is focused on relapse and will include:- A genomic characterisation at first diagnosis and relapse of AML and bone marrow cells,
– A study of the evolution of drug sensitivity between initial diagnosis and relapse,
– An identification of new prognostic markers to improve our ability to identify the patients most at risk of relapse. Prognostic markers are clinical signs that allow us to differentiate one patient group from another (such as the presence of a protein, a specific genomic alternation…).
In conclusion, this project is based on a multi-approach research in order to (i) improve the characterisation of the relapse and resistance mechanisms, (ii) discover new targeted drugs and (iii) understand the evolution of the treatment’s sensitivity with the ultimate goal to improve the patients’ outcome through a personalisation of the therapeutic strategies.Financed: 499 000 €Duration: 2 yearsCountries: France (centres of Paris, Lyon and Marseille)Disease: Acute myeloid leukaemiaStatus: Ongoing
EpiRT program on rhabdoid tumors
Rhabdoid tumours are rare aggressive cancers affecting young children. They mainly occur in the brain, but also in the kidney, liver, …Survival rate for the patients with this tumour is under 50% and those surviving will have to go on with their life with oftentimes severe long-term side effects caused by their treatment.
These tumours are characterised by the loss of one unique gene, called SMARCB1. This gene acts to remodel the chromatin and modifies the way the DNA strand is packaged in the cell nuclei. Since there is no other gene defect, SMARCB1 constitutes the only direct targetable gene in this disease.
SMARCB1 is gifted with a very much “epi-genetic” character. Therefore, one major field of research for further therapeutic development concerns drugs that also target epigenetic actors. Epigenetics is the science which explains gene coding: it allows us to understand why cells with the same genetic code have different functions inside someone’s body. Think about a very long book from which some words would be highlighted in different colours to create several alternative plots.
This project will focus on the role of one epigenetic drug in rhabdoid tumours, inhibiting the epigenetic protein “EZH2”, which inhibition has shown some preliminary effects in the clinics.
The impact of the drug on rhabdoid tumours will be analysed at the cell level when grafted in mice. The impact of this drug on the immune environment will also be studied.Financed: 500 000 €Duration: 2 yearsCountries: France & GermanyDisease: Rhabdoid tumourStatus: Ongoing
IMAGINE program on osteosarcomas
Osteosarcoma is a very challenging paediatric tumour in oncology. It is the most common bone cancer in children, adolescents and young adults (10 to 14%). In the last 30 years, there have been no improvements in treatment despite a survival rate of 20% in those children who develop metastasis.Immunotherapy is a treatment that attempts to strengthen the natural ability of the immune system to fight cancer.
Also described as “living drugs”, white blood cells (immune effector cells) will be isolated and genetically manipulated to express a specific receptor against the tumour cells. These receptors allow white blood cells to recognise tumour cells and destroy them.
In other words, tumour cells that could stay inside a patient’s body “incognito”, like any other healthy cell, will now be identified by the white blood cells as harmful cells that must be eliminated.These therapies have led to spectacular results in blood cancer, both for paediatric and adult patients who had no more other treatment options.However, to this day, it has not been possible to replicate this success in patients with solid tumours like osteosarcomas. This is mainly due to the barrier posed by the hostile microenvironment surrounding the tumour. This barrier prevents the migration of white blood cells and diminishes their capacity to fight a tumour.
The “IMAGINE” project aims at overcoming this barrier in paediatric osteosarcoma using an innovative, inexpensive, non-invasive and easy to implement approach.
White blood cells will be loaded with magnetic nanoparticles that can be guided to the tumour through a magnetic field. With such magnetic wings, the therapeutic efficacy of those cells will be considerably enhanced!
This approach not only will increase the concentration of white blood cells at the tumour site but will minimise toxicities on healthy tissues which is one of the main concerns with current therapies (chemotherapy). If the IMAGINE project’s results are conclusive, the next step will consist in the opening of an early phase clinical trial to test this technology in order to increase the survival rates and quality of life of young patients with osteosarcoma.Financed: 500 000 €Duration: 2 yearsCountries: Spain, France & NorwayDisease: OsteosarcomaStatus: Ongoing
RESTRAIN program on neuroblastoma
Neuroblastoma is a tumour that mainly occurs in young children and derives from nerve cells located in the abdomen or next to the spine. The chances of survival for children with the aggressive form of this disease are very small. In addition, children who survive the disease often suffer later in life from health problems as a result of the treatment.The projects’ researchers recently identified a key protein denoted as RRM2 that neuroblastoma cells rely on for sustained growth.
In this project “RESTRAIN”, researchers will create mouse and zebrafish models to cause a degradation of the RRM2 protein with the objective to improve our understanding of the role of RRM2 during neuroblastoma tumour formation. These novel preclinical models will also be explored to identify synergistic novel drugging strategies by using available small molecules.In addition, the objective is to discover as many other proteins as possible that together with RRM2 play a crucial role in neuroblastoma cells and thus serve as novel targets for future therapy.This project aims at identifying news treatment options for children with neuroblastoma. As a result, the project will benefit all children if the study’s conclusions are encouraging.Financed: 500 000 €Duration: 2 yearsCountries: Belgium and United KingdomDisease: NeuroblastomaStatus: Ongoing
Programme support and management is provided by the European Science Foundation, which is the intermediary with the funding organisations.
For further information about this announcement of opportunity please contact:
Fight Kids Cancer secretariat at ESF: email@example.com