Liu Meijun, Wang Yuying, Chen Xiaoli, Zeng Yu, Huang Wenqiong, Yang Jiawen, Dai Hong, Cheng Lixin, Mauro Claudio, Cheung Kenneth Chat Pan
Phenome Research Center, Hong Kong Baptist University, Kowloon, Hong Kong, China.
School of Life Science, Southern University of Science and Technology, Shenzhen, Guangdong Province, China.
Clin Epigenetics. 2025 Jun 21;17(1):108. doi: 10.1186/s13148-025-01900-5.
Glioblastoma multiforme (GBM) is a lethal brain tumor. With the current gold standard chemotherapy treatment, temozolomide (TMZ), many patients do not survive beyond one year. While the urgency of researching novel treatments is understandable, the prohibitively high costs and the prolonged duration of research and clinical trials significantly delay the availability of medical advancements to the general public. This highlights the urgent need for adjuvant therapies to enhance treatment effectiveness.
Recent research has suggested the potential of repurposing FDA-approved drugs such as temozolomide (TMZ), disulfiram (DSF), and aspirin for the treatment of glioblastoma, with encouraging evidence particularly for DSF and aspirin. Additionally, compounds like histone deacetylase inhibitors (e.g., vorinostat) are being investigated for their impact on non-coding RNA (ncRNA) modulation, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Combining traditional therapies with ncRNA modulation has shown potential in enhancing therapeutic efficacy and targeting specificity. NcRNAs play a crucial role in regulating gene expression and have been implicated in tumor growth, invasion, and treatment resistance. Recent discoveries, such as cuproptosis, offer new insights into tumor cell death mechanisms.
This review focuses on how these molecular insights can serve as novel therapeutic targets and how drug adjuvant therapy may improve GBM treatment strategies. It focuses on how the integration of ncRNA modulation with conventional therapies and the combination strategy of enhancing efficacy of drugs can enhance treatment efficacy and pave the way for innovative approaches in managing GBM. In short, we will explore how non-coding RNAs (ncRNAs) might serve as promising targets and how repurposing TMZ, DSF, and aspirin could help enhance the efficacy of GBM treatment.
多形性胶质母细胞瘤（GBM）是一种致命的脑肿瘤。采用当前的金标准化疗药物替莫唑胺（TMZ）进行治疗，许多患者存活时间不超过一年。虽然研究新型治疗方法的紧迫性是可以理解的，但过高的成本以及研究和临床试验的漫长周期严重延迟了医学进步成果向普通大众的普及。这凸显了迫切需要辅助疗法来提高治疗效果。
最近的研究表明，重新利用美国食品药品监督管理局（FDA）批准的药物如替莫唑胺（TMZ）、双硫仑（DSF）和阿司匹林来治疗胶质母细胞瘤具有潜力，尤其是DSF和阿司匹林有令人鼓舞的证据。此外，组蛋白去乙酰化酶抑制剂（如伏立诺他）等化合物正在被研究对非编码RNA（ncRNA）调节的影响，包括微小RNA（miRNA）和长链非编码RNA（lncRNA）。将传统疗法与ncRNA调节相结合已显示出提高治疗效果和靶向特异性的潜力。ncRNA在调节基因表达中起关键作用，并与肿瘤生长、侵袭和治疗抗性有关。最近的发现，如铜死亡，为肿瘤细胞死亡机制提供了新的见解。
本综述重点关注这些分子见解如何作为新的治疗靶点，以及药物辅助疗法如何改善GBM的治疗策略。重点关注ncRNA调节与传统疗法的整合以及增强药物疗效的联合策略如何提高治疗效果，并为GBM的管理创新方法铺平道路。简而言之，我们将探讨非编码RNA（ncRNA）如何可能成为有前景的靶点，以及重新利用TMZ、DSF和阿司匹林如何有助于提高GBM的治疗效果。
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