Advancing brain tumor therapy: unveiling the potential of PROTACs for targeted protein degradation

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Abstract
The long-term treatment of malignancies, particularly brain tumors, is challenged by abnormal protein expression and drug resistance. In terms of potency, selectivity, and overcoming drug resistance, Proteolysis Targeting Chimeras (PROTACs), a cutting-edge method used to selectively degrade target proteins, beats traditional inhibitors. This review summarizes recent research on using PROTACs as a therapeutic strategy for brain tumors, focusing on their mechanism, benefits, limitations, and the need for optimization. The review draws from a comprehensive search of peer-reviewed literature, scientific databases, and clinical trial databases. Articles published up to the knowledge cutoff date up to 14 April 2023 were included. Inclusion criteria covered PROTAC-based brain tumor therapies, including preclinical and early clinical studies, with no restrictions on design or publication type. We included studies using in vitro, in vivo brain tumor models, and human subjects. Eligible treatments involved PROTACs targeting proteins linked to brain tumor progression. We evaluated the selected studies for methodology, including design, sample size, and data analysis techniques. A narrative synthesis summarized key outcomes and trends in PROTAC-based brain tumor therapy. Recent research shows PROTACs selectively degrade brain tumor-related proteins with minimal off-target effects. They offer enhanced potency, selectivity, and the ability to combat resistance compared to traditional inhibitors. PROTACs hold promise for brain tumor treatment offering advantages over traditional inhibitors, but more research is needed to refine their mechanisms, efficacy, and safety. Larger-scale trials and translational studies are essential for assessing their clinical utility.

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