Year: 2025
Type: article
Abstract: High-grade gliomas (HGGs) are deadly primary brain tumours in pediatric and adults with the lowest survival rates in allcancer (< 10%). The Research Consortium for Neuro-oncology (ReCoN) is a team consist of clinicians and researchers in BC Cancer and Vancouver General Hospital aiming to identify disease mechanisms of poorly defined “histone H3- and IDH-WT” HGGs. The study aims to accelerate the derivation of patient-specific avatar glioma models, agnostically nominate therapeutic targets through genomics, and to empirically evaluate therapeutic efficacy/cytotoxicity using patient-derived cell models. As a proof-of-concept study, 12 primary resected grade IV glioblastoma tumour and tumour-derived cell models will undergo matched molecular profiling, including long read whole genome sequencing and single cell ATAC- and RNA-seq. Computational tools such as GRETTA will be used to nominate targetable genetic network vulnerabilities via small molecule compounds. The nominated compounds will be evaluated for efficacy/cytotoxicity using patient-derived models. Through this pilot, we aim to develop an end-to-end workflow to enhance the detection of driver mutations and design of driver-specific therapies in “WT” HGGs to improve patient-specific care.
Source: Neuro-Oncology Advances
Authors: Pariya Azarafshar, Hannah Schoenroth, Dan Jin, Yuka Takemon, Kira Tosefsky, Tiffany Chang, Diane Trinh, Melanie Bailey, Richard Corbett, Nigel O’Neil, Amanda Kotzer, Serge Makarenko, Peter Stirling, Poul Sorensen, Manik Chahal, Rebecca Harrison, Stephen Yip, Marco Marra, Mostafa Fatehi, Carol C L Chen
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,615
OpenAlex ID: W4413856491