Indolent or refractory neuroblastoma is a clinically well-known sub-type of the disease. It shows little or no response to currently available first-line treatments, remains stable for some time before eventually beginning to progress. It often affects older children and young adults, giving them a prolonged battle with the disease, and with very poor overall survival.
Until now, this group of patients has been somewhat overlooked within research. Indeed, most options for innovative treatments have been part of non-specific trials designed for cases of relapsed or refractory neuroblastoma. Unfortunatelyy, these often have shown little benefit for those with indolent disease.
A major hurdle to improving outcomes for these patients has been the inability to define this type of disease at a molecular level. Consequently, overcoming this hurdle would enable them to be identified at diagnosis. Indeed, this is an obstacle this new research is seeking to address.
“Putting your child through round after round of chemotherapy and watching them suffer from all the horrible side-effects only to find it’s made no difference to their disease is a truly devastating blow for parents. We have to identify who these children are at diagnosis so we can spare them from toxic chemotherapies that do not work, and then we have to find better ways to treat their disease instead. This grant call is about making those all-important first strides towards better treatments, and taking a stand for these children and their families.” .
Within this project, the researchers have 3 key aims to address the unmet needs of these children and young people :
- Develop a clinical tool which can detect biomarkers for indolent neuroblastoma, with hopes to use this to identify these patients at diagnosis. This will be based on so-called Telomere Maintenance Mechanisms that drive tumour growth, in particular Alternative Lengthening of Telomeres (ALT) and ATRX.
- Create robust laboratory models of the sub-group which do not currently exist and will provide a strong basis for any future research in this area.
- Look at preclinical testing of small molecule therapies in combination with existing immunotherapy in the hopes of finding better responses from the highly treatment-resistant disease.
At the end of two years the team hope to have a new clinical trial for this group of patients ready to take forward for funding.
This research project involves a transatlantic collaboration between several research centers and hospitals:
Children’s Hospital of Philadelphia (CHOP) , Icahn School of Medicine at Mount Sinai in New-York, Institute of Cancer Research, London; Texas Tech University Health Sciences Center, Seattle Children’s Hospital and Princess Máxima Center in the Netherlands.