Liu Peng, Griffiths Scott, Veljanoski Damjan, Vaughn-Beaucaire Philippa, Speirs Valerie, Brüning-Richardson Anke
Institute of Medical Sciences, School of Medicine Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
Aberdeen Royal Infirmary, Foresterhill Health Campus, Aberdeen, UK.
Expert Rev Mol Med. 2021 Dec 2;23:e20. doi: 10.1017/erm.2021.20.
Glioblastoma (GBM) is the most common and aggressive primary brain tumour, yet little progress has been made towards providing better treatment options for patients diagnosed with this devastating condition over the last few decades. The complex nature of the disease, heterogeneity, highly invasive potential of GBM tumours and until recently, reduced investment in research funding compared with other cancer types, are contributing factors to few advancements in disease management. Survival rates remain low with less than 5% of patients surviving 5 years. Another important contributing factor is the use of preclinical models that fail to fully recapitulate GBM pathophysiology, preventing efficient translation from the lab into successful therapies in the clinic. This review critically evaluates current preclinical GBM models, highlighting advantages and disadvantages of using such models, and outlines several emerging techniques in GBM modelling using animal-free approaches. These novel approaches to a highly complex disease such as GBM show evidence of a more truthful recapitulation of GBM pathobiology with high reproducibility. The resulting advancements in this field will offer new biological insights into GBM and its aetiology with potential to contribute towards the development of much needed improved treatments for GBM in future.
胶质母细胞瘤(GBM)是最常见且侵袭性最强的原发性脑肿瘤,然而在过去几十年里,对于被诊断患有这种毁灭性疾病的患者,在提供更好的治疗方案方面进展甚微。该疾病的复杂性、异质性、GBM肿瘤的高度侵袭潜力,以及直到最近与其他癌症类型相比研究资金投入减少,都是导致疾病管理进展甚微的因素。生存率仍然很低,不到5%的患者能存活5年。另一个重要的促成因素是临床前模型未能完全重现GBM的病理生理学,从而阻碍了从实验室到临床成功治疗的有效转化。本综述批判性地评估了当前的临床前GBM模型,强调了使用此类模型的优缺点,并概述了几种使用无动物方法进行GBM建模的新兴技术。这些针对GBM等高度复杂疾病的新方法显示出更真实地重现GBM病理生物学且具有高可重复性的证据。该领域由此取得的进展将为GBM及其病因学提供新的生物学见解,有可能为未来开发急需的GBM改进治疗方法做出贡献。