Gillies McIndoe Research Institute, Newtown, Wellington, 6021, New Zealand.
Centre for Biodiscovery and School of Biological Sciences, Victoria University of Wellington, Kelburn, Wellington, 6021, New Zealand.
J Transl Med. 2024 Jun 6;22(1):540. doi: 10.1186/s12967-024-05301-9.
The adaptability of glioblastoma (GBM) cells, encouraged by complex interactions with the tumour microenvironment (TME), currently renders GBM an incurable cancer. Despite intensive research, with many clinical trials, GBM patients rely on standard treatments including surgery followed by radiation and chemotherapy, which have been observed to induce a more aggressive phenotype in recurrent tumours. This failure to improve treatments is undoubtedly a result of insufficient models which fail to incorporate components of the human brain TME. Research has increasingly uncovered mechanisms of tumour-TME interactions that correlate to worsened patient prognoses, including tumour-associated astrocyte mitochondrial transfer, neuronal circuit remodelling and immunosuppression. This tumour hijacked TME is highly implicated in driving therapy resistance, with further alterations within the TME and tumour resulting from therapy exposure inducing increased tumour growth and invasion. Recent developments improving organoid models, including aspects of the TME, are paving an exciting future for the research and drug development for GBM, with the hopes of improving patient survival growing closer. This review focuses on GBMs interactions with the TME and their effect on tumour pathology and treatment efficiency, with a look at challenges GBM models face in sufficiently recapitulating this complex and highly adaptive cancer.
脑胶质瘤（GBM）细胞的适应性，加上与肿瘤微环境（TME）的复杂相互作用，目前使 GBM 成为一种无法治愈的癌症。尽管进行了大量的研究，并进行了许多临床试验，但 GBM 患者仍依赖于标准治疗，包括手术加放疗和化疗，这些治疗方法已被观察到会在复发性肿瘤中诱导更具侵袭性的表型。治疗效果没有改善，这无疑是由于缺乏能够纳入人脑 TME 成分的模型所致。研究越来越多地揭示了肿瘤-TME 相互作用的机制，这些机制与患者预后恶化相关，包括肿瘤相关星形胶质细胞线粒体转移、神经元回路重塑和免疫抑制。这种被肿瘤劫持的 TME 高度参与了耐药性的产生，治疗暴露后 TME 和肿瘤内的进一步改变导致肿瘤生长和侵袭增加。最近在改善类器官模型方面的进展，包括 TME 的各个方面，为 GBM 的研究和药物开发铺平了令人兴奋的未来，患者生存的希望越来越大。本文综述了 GBM 与 TME 的相互作用及其对肿瘤病理学和治疗效果的影响，并探讨了 GBM 模型在充分再现这种复杂且高度适应性癌症方面所面临的挑战。
