Identifying Novel Targets in Paediatric High Grade Glioma

Paediatric high-grade gliomas (pHGG) represent some of the most deadly brain cancers in children, differing significantly from adult gliomas in location and genetic characteristics. They are notorious for their aggressive behavior and poor response to traditional treatments. Understanding their genetic makeup is pivotal for developing targeted therapies. The advent of the CRISPR-Cas system has transformed genetic research, allowing precise genome editing and the creation of comprehensive maps of cancer dependencies. This project employs combinatorial CRISPR-Cas12 screening to unravel intricate genetic interactions within pHGG. By simultaneously targeting multiple genes, this approach uncovers synergistic or antagonistic relationships, potentially identifying key genetic drivers and vulnerabilities. Additionally, it sheds light on the tumors' resistance mechanisms, informing the development of personalized therapies. With access to numerous patient-derived cell lines, this project has the potential to revolutionize pHGG treatment by uncovering critical genetic interactions and paving the way for targeted therapies.