Ibrahim Saooda, Khan Muhammad Umer, Noreen Saadia, Firdous Safia, Khurram Iqra, Rehman Raima, Javed Muhammad Arshad, Ali Qurban
Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan.
Faculty of Rehabilitation and Allied Health Sciences, Riphah International University, Lahore, Pakistan.
Cytotechnology. 2025 Apr;77(2):54. doi: 10.1007/s10616-025-00716-8. Epub 2025 Jan 31.
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.
恶性肿瘤，尤其是脑肿瘤的长期治疗面临着蛋白质异常表达和耐药性的挑战。在效力、选择性和克服耐药性方面，蛋白酶靶向嵌合体（PROTACs）作为一种用于选择性降解靶蛋白的前沿方法，优于传统抑制剂。本综述总结了近期关于使用PROTACs作为脑肿瘤治疗策略的研究，重点关注其作用机制、益处、局限性以及优化的必要性。该综述通过全面检索同行评审文献、科学数据库和临床试验数据库得出。纳入截至2023年4月14日知识截止日期发表的文章。纳入标准涵盖基于PROTAC的脑肿瘤治疗，包括临床前和早期临床研究，对设计或发表类型无限制。我们纳入了使用体外、体内脑肿瘤模型和人类受试者的研究。符合条件的治疗涉及靶向与脑肿瘤进展相关蛋白质的PROTACs。我们评估了所选研究的方法，包括设计、样本量和数据分析技术。叙述性综合总结了基于PROTAC的脑肿瘤治疗的关键结果和趋势。近期研究表明，PROTACs能以最小的脱靶效应选择性降解脑肿瘤相关蛋白。与传统抑制剂相比，它们具有更高的效力、选择性以及对抗耐药性的能力。PROTACs在脑肿瘤治疗方面具有前景，相较于传统抑制剂具有优势，但需要更多研究来完善其作用机制、疗效和安全性。大规模试验和转化研究对于评估其临床效用至关重要。
