研究动态
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对于建模散发高级别胶质瘤和开发临床相关治疗方案的考虑。

Considerations for modelling diffuse high-grade gliomas and developing clinically relevant therapies.

发表日期:2023 Apr 01
作者: Sarah L Higginbottom, Eva Tomaskovic-Crook, Jeremy M Crook
来源: Stem Cell Research & Therapy

摘要:

高强度弥漫性胶质瘤是一些最危险的人类癌症之一,缺乏治愈的治疗选择。2021年世界卫生组织对胶质瘤进行的最新分子分类预计将通过针对特定肿瘤类型开发治疗方案,提高神经肿瘤患者的疗效。尽管如此,缺乏能够重新创造异质性和细胞表型的大脑微环境中存在的肿瘤的前临床模型平台阻碍了研究的进行。微环境为影响增殖,存活和基因表达的肿瘤细胞亚群提供线索,从而改变对治疗干预的易感性。因此,传统体外细胞模型在转录水平和分化状态不同的这些多样化细胞状态下对化疗和放疗的反应很差。为了改善传统模型平台的相关性,最近的关注集中在基于人类多能干细胞的和组织工程技术上,例如三维(3D)生物打印和微流体设备。适当应用这些令人激动的新技术,考虑到肿瘤异质性和微环境相互作用,有望开发更适用的模型和临床相关疗法。这样做,我们将有更好的机会将前临床研究结果转化为患者人群,从而解决当前可怜的肿瘤临床试验成功率。 ©2023。作者。
Diffuse high-grade gliomas contain some of the most dangerous human cancers that lack curative treatment options. The recent molecular stratification of gliomas by the World Health Organisation in 2021 is expected to improve outcomes for patients in neuro-oncology through the development of treatments targeted to specific tumour types. Despite this promise, research is hindered by the lack of preclinical modelling platforms capable of recapitulating the heterogeneity and cellular phenotypes of tumours residing in their native human brain microenvironment. The microenvironment provides cues to subsets of glioma cells that influence proliferation, survival, and gene expression, thus altering susceptibility to therapeutic intervention. As such, conventional in vitro cellular models poorly reflect the varied responses to chemotherapy and radiotherapy seen in these diverse cellular states that differ in transcriptional profile and differentiation status. In an effort to improve the relevance of traditional modelling platforms, recent attention has focused on human pluripotent stem cell-based and tissue engineering techniques, such as three-dimensional (3D) bioprinting and microfluidic devices. The proper application of these exciting new technologies with consideration of tumour heterogeneity and microenvironmental interactions holds potential to develop more applicable models and clinically relevant therapies. In doing so, we will have a better chance of translating preclinical research findings to patient populations, thereby addressing the current derisory oncology clinical trial success rate.© 2023. The Author(s).