Mahdi Asma, Aittaleb Mohamed, Tissir Fadel
College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Education City, Doha P.O. Box 5825, Qatar.
Cells. 2025 May 6;14(9):675. doi: 10.3390/cells14090675.
Glioblastoma (GBM), or grade 4 glioma, is the most common and aggressive primary brain tumor in adults with a median survival of 15 months. Increasing evidence suggests that GBM's aggressiveness, invasiveness, and therapy resistance are driven by glioma stem cells (GSCs), a subpopulation of tumor cells that share molecular and functional characteristics with neural stem cells (NSCs). GSCs are heterogeneous and highly plastic. They evade conventional treatments by shifting their state and entering in quiescence, where they become metabolically inactive and resistant to radiotherapy and chemotherapy. GSCs can exit quiescence and be reactivated to divide into highly proliferative tumor cells which contributes to recurrence. Understanding the molecular mechanisms regulating the biology of GSCs, their plasticity, and the switch between quiescence and mitotic activity is essential to shape new therapeutic strategies. This review examines the latest evidence on GSC biology, their role in glioblastoma progression and recurrence, emerging therapeutic approaches aimed at disrupting their proliferation and survival, and the mechanisms underlying their resistance to therapy.
胶质母细胞瘤（GBM），即4级胶质瘤，是成人中最常见且侵袭性最强的原发性脑肿瘤，中位生存期为15个月。越来越多的证据表明，GBM的侵袭性、浸润性和治疗抗性是由胶质瘤干细胞（GSCs）驱动的，GSCs是肿瘤细胞的一个亚群，与神经干细胞（NSCs）具有共同的分子和功能特征。GSCs具有异质性且高度可塑性。它们通过改变自身状态进入静止期来逃避传统治疗，在静止期它们代谢不活跃，对放疗和化疗具有抗性。GSCs可以从静止期退出并重新激活，分裂为高度增殖的肿瘤细胞，这导致了肿瘤复发。了解调节GSCs生物学特性、其可塑性以及静止期和有丝分裂活性之间转换的分子机制对于制定新的治疗策略至关重要。本综述探讨了关于GSCs生物学特性的最新证据、它们在胶质母细胞瘤进展和复发中的作用、旨在破坏其增殖和存活的新兴治疗方法以及它们对治疗产生抗性的潜在机制。
