The Brain Tumor Translational Laboratory, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico.
Mol Cancer Res. 2023 Aug 1;21(8):755-767. doi: 10.1158/1541-7786.MCR-23-0048.
The treatment of the most aggressive primary brain tumor in adults, glioblastoma (GBM), is challenging due to its heterogeneous nature, invasive potential, and poor response to chemo- and radiotherapy. As a result, GBM inevitably recurs and only a few patients survive 5 years post-diagnosis. GBM is characterized by extensive phenotypic and genetic heterogeneity, creating a diversified genetic landscape and a network of biological interactions between subclones, ultimately promoting tumor growth and therapeutic resistance. This includes spatial and temporal changes in the tumor microenvironment, which influence cellular and molecular programs in GBM and therapeutic responses. However, dissecting phenotypic and genetic heterogeneity at spatial and temporal levels is extremely challenging, and the dynamics of the GBM microenvironment cannot be captured by analysis of a single tumor sample. In this review, we discuss the current research on GBM heterogeneity, in particular, the utility and potential applications of fluorescence-guided multiple sampling to dissect phenotypic and genetic intra-tumor heterogeneity in the GBM microenvironment, identify tumor and non-tumor cell interactions and novel therapeutic targets in areas that are key for tumor growth and recurrence, and improve the molecular classification of GBM.
由于其异质性、侵袭性和对化疗和放疗的不良反应，成人中最具侵袭性的原发性脑肿瘤——胶质母细胞瘤（GBM）的治疗极具挑战性。因此，GBM 不可避免地会复发，只有少数患者在诊断后能存活 5 年。GBM 的特征是广泛的表型和遗传异质性，形成了多样化的遗传景观和亚克隆之间的生物相互作用网络，最终促进肿瘤生长和治疗耐药性。这包括肿瘤微环境中的时空变化，影响 GBM 中的细胞和分子程序以及治疗反应。然而，在时空水平上剖析表型和遗传异质性极具挑战性，而且单个肿瘤样本的分析无法捕捉 GBM 微环境的动态。在这篇综述中，我们讨论了 GBM 异质性的当前研究，特别是荧光引导多次采样在剖析 GBM 微环境中肿瘤内表型和遗传异质性、识别肿瘤和非肿瘤细胞相互作用以及新的治疗靶点方面的实用性和潜在应用，这些靶点对于肿瘤生长和复发的关键区域至关重要，并提高了 GBM 的分子分类。
