PCM-18: PAEDIATRIC BRAIN TUMOUR PRE-CLINICAL MODELS ENCYCLOPAEDIA: A COLLABORATIVE PROJECT PROPOSAL

While pre-clinical models of children's brain tumours are widely-used to test tumour biology and prioritise compounds for clinical trials their predictive value has been disappointing. As tumours are split into molecular subgroups it is becoming increasingly important to use well-characterised pre-clinical tools and match them to patients' tumours. For example, in medulloblastoma the D283 cell-line has been classified as both Group 3 and 4 by different authors and most animal models of Group 3 cluster with the SHH group. This biological uncertainty translates to unreliable predictions and necessitates using multiple models in an unfocused manner. A systematic Web-of-Science search for medulloblastoma cell-lines revealed that almost all medulloblastoma cell-lines cluster with either SHH or myc-amplified Group 3 medulloblastoma, with only two available for Group 4 and one for WNT tumours. From the animal models, only three develop metastases (Sleeping beauty, Smo/Smo and GTML) and there are no models for 50% of medulloblastomas (Group 4 and p53wt WNT). This proof-of-concept review sets the foundation for a collaborative systematic review project of the pre-clinical models available in children's brain tumours. The project will yield a publication arranging the available information in the literature and will feature a matched website to create online “pre-clinical model passports”. These passports will summarise and link to the evidence about the brain tumour and subtype affiliation of the model along with authentication, gene and protein expression profiles. This work will translate novel medicines to clinical trials quicker and will enable researchers to convincingly link models and patients.