PROTACs in Treatment of Glioma

Treatment for gliomas, especially glioblastoma (GBM), is extremely difficult because of the disease’s poor prognosis and low 5-year survival rate (less than 5%). There is an urgent need for novel strategies because existing treatments have not been able to provide long-term solutions. Proteolysis-targeting chimeras (PROTACs) present a potential approach since they utilize the ubiquitin-proteasome system to degrade particular proteins that are essential for the growth and dissemination of gliomas. Targeting oncogenic proteins necessary for glioma survival, PROTACs interfere with critical mechanisms that promote tumor growth. PROTAC treatment targets the epidermal growth factor receptor (EGFR), which is often dysregulated in gliomas. By destroying mutant EGFR variants, PROTACs may be able to overcome resistance that is frequently seen with conventional targeted therapies, therefore improving therapy efficacy as a whole. Furthermore, the complex and diverse biology of gliomas is addressed by PROTACs’ capacity to target many proteins at once, which may delay the formation of resistance. Important information on PROTACs’ translational potential is provided by ongoing clinical trials evaluating the safety and effectiveness of the treatment in glioma patients. In the end, glioma treatment that uses targeted protein degradation to interfere with neoplastic pathways is called PROTAC therapy. In the context of glioblastoma and its pivotal signaling pathways such as EGFR, TGF-b, and p53, this chapter will delve into the role of E3 ubiquitin ligases and deubiquitinating enzymes, offering fresh perspectives on their therapeutic utility for glioblastoma.