Neuroblastoma (NB) – the current state of the art

Neuroblastoma (NB) is a cancer of early childhood that arises from the developing sympathetic nervous system. Primary NB tumours commonly arise in the adrenal medulla, while metastases often spread to regional lymph nodes, bone and bone marrow. The prevalence is about 1 in 7,000 live births and despite its relative rareness it exacts a devastating toll, accounting for 10% of childhood cancer mortality. NB displays a broad clinical heterogeneity ranging from patients with spontaneously regressing tumours to those displaying an aggressive metastatic disease with tumours prone to resistant relapses despite intensive multimodal therapy. It is therefore of great importance to be able to identify patients that need aggressive therapy and patients that will thrive without in order to minimize side-effects from treatment in this group. NB tumours with a favourable outcome are likely to have near-triploid karyotypes with few or no segmental changes, whereas aggressive tumours often exhibit near-diploid/tetraploid karyotypes and chromosomal rearrangements, such as MYCN-amplification, deletion of 11q and gain of 17q. Only a limited number of recurrent gene mutations have been identified, using new whole genome sequencing strategy, including alterations in ARID1A/ARID1B, ATRX and ALK2-4.

Neuroblastoma (NB) – where we want to be in 5 years

As a result of the work proposed in this SSF application we aim to achieve the following:

All NB patients will be sampled for biological material at diagnosis and repeatedly during treatment at the DNA/RNA level for a battery of clinically relevant biomarkers, including genomic pattern, sequencing and detailed analysis of e.g. ALK, MYCN, NBAT-1, WIP1 and others as yet identified.

Biomarkers for use in assessment of patient response as well as identification of relapse will be available for clinical use in NB patients within national and international NB studies as carried out by VSTB, NOPHO, SIOPEN and other clinical collaborative groups.

Novel biomarkers suitable for therapeutic use will have been identified, verified and developed/under development.

Biomarkers will be incorporated into clinical stratification and tailoring of clinical therapy.

Detailed biological information will be used for early use of targeted therapies and implementation of experimental trials at relapse and/or resistant disease.

Specific therapeutic targets e.g. NBAT-1, Wip1, ALK/ERK5 are under development and/or in early clinical phases.

Knowledge obtained within this project will have been implementated in translational efforts for other diseases including other childhood tumours included in the national biobank (BTB, Barntumörbanken) and the national registry and specifically lung cancer (ALK-targeted therapies), breast and ovarian cancer (Wip1-targeted therapies) and tumours of the CNS, in particular medulloblastoma (Wip1 and NBAT-1 targeted therapies).