Glioblastoma (GBM) is the most common and devastating primary brain tumor, leading to a uniform fatality after diagnosis. A major difficulty in eradicating GBM is the presence of microscopic residual infiltrating disease remaining after multimodality treatment. Glioma cancer stem cells (CSCs) have been pinpointed as the treatment-resistant tumor component that seeds ultimate tumor progression. Despite the key role of CSCs, the ideal preclinical model to study the genetic and epigenetic landmarks driving their malignant behavior while simulating an accurate interaction with the tumor microenvironment (TME) is still missing. The introduction of three-dimensional (3D) tumor platforms, such as organoids and 3D bioprinting, has allowed for a better representation of the pathophysiologic interactions between glioma CSCs and the TME. Thus, these technologies have enabled a more detailed study of glioma biology, tumor angiogenesis, treatment resistance, and even performing high-throughput screening assays of drug susceptibility. First, we will review the foundation of glioma biology and biomechanics of the TME, and then the most up-to-date insights about the applicability of these new tools in malignant glioma research.

胶质母细胞瘤（GBM）是最常见和破坏性最大的原发性脑肿瘤，诊断后导致均匀的死亡。根除GBM的主要困难是在多模态治疗后仍存在微观残留浸润性疾病。胶质瘤癌症干细胞（CSCs）已被明确定位为治疗性肿瘤成分，可播种最终肿瘤。尽管CSC发挥着关键作用，但仍缺乏理想的临床前模型来研究驱动其恶性行为的遗传和表观标志，同时模拟与肿瘤微环境（TME）的精确相互作用。三维（3D）肿瘤平台（例如类器官和3D生物打印）的引入，使神经胶质瘤CSC与TME之间的病理生理相互作用得以更好地体现。从而，这些技术可以对神经胶质瘤生物学，肿瘤血管生成，治疗耐药性进行更详细的研究，甚至可以进行药物敏感性的高通量筛选测定。首先，我们将回顾TME胶质瘤生物学和生物力学的基础，然后是关于这些新工具在恶性胶质瘤研究中的适用性的最新见解。