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Neuroblastoma, the most prevalent cancer in infants, arises from neural crest cells and can manifest as tumours in various parts of the body. High-risk neuroblastoma patients face unfavourable prognosis and exhibit poor response to current therapies, emphasising the critical need for identifying more effective therapeutic targets. To identify potential targets in a comprehensive manner, my research will explore the resistance mechanisms of neuroblastoma to VENCLEXTA® (venetoclax), a treatment currently undergoing clinical trials for high-risk neuroblastoma. Utilizing CRISPRi screening technology,we aim to identify targets for new PROTACs that can sensitize neuroblastoma to venetoclax treatment and improve clinical outcome. Exploring these targets and harnessing the ubiquitin system could potentially reveal synergistic effects, ultimately enhancing the effectiveness of venetoclax treatment in neuroblastoma. Overall, this project aims to reveal the molecular mechanisms involved in neuroblastoma and pave the way for targeted therapeutic interventions, ultimately striving to improve patient outcomes. |