Drug Discovery Scientist - Industrial PhD Candidate Oncoheroes Biosciences Vilassar De Mar, Catalonia, Spain
Abstract: Pediatric brain tumors (PBTs) represent about 25% of all pediatric cancers and are the most common solid tumors in children and adolescents. Medulloblastoma (MB) is the most frequently occurring malignant PBT, accounting for almost 10% of all pediatric cancer deaths. MB Group 3 (MB G3) accounts for 25-30% of all MB cases and has the worst outcome, particularly when associated with MYC amplification. However, no targeted treatments for this group have been developed so far.
Here we describe a unique high throughput screening (HTS) platform designed to identify new therapies for MB G3. The platform incorporates optimized and validated reproducible 2D and 3D efficacy and toxicity models, that account for tumor heterogenicity, limited efficacy and unacceptable toxicity from the very early stage of drug development. The platform has been validated by conducting a pilot HTS campaign with a 1280 lead-like compound library. Results showed 8 potential candidates, all compounds targeted MB reported targets and several are currently approved or in clinical trials for pediatric patients with PBTs, including MB. Moreover, hits were then combined to identify potential synergistic combinations to avoid tumor resistance, identifying 3 synergistic pairs, one currently being studied in the clinics for recurrent MB and other PBTs.
