多形性胶质母细胞瘤（GBM）是最常见的成人原发性脑肿瘤。 GBM 的标准临床治疗包括最大程度的手术切除，以及伴随的放疗 (RT) 和替莫唑胺 (TMZ) 化疗以及辅助 TMZ 周期。尽管该方案很严重，但 GBM 具有高度耐药性，并且在几乎所有病例中都会复发，而该方案自 2005 年以来一直保持不变。有限扩散或慢性缺氧已被确定为驱动这种侵袭性表型的主要因素之一。肿瘤体内缺氧的存在有助于激活缺氧诱导因子（HIF）介导的缺氧信号通路，进而激活生物机制以确保GBM在有限的氧气和营养供应下的适应和生存。激活的下游途径涉及维持干细胞样表型，诱导间充质转移、侵袭和迁移，改变细胞和氧代谢，以及增加血管生成、自噬和免疫抑制。因此，在这篇综述中，我们将讨论最近的临床前和临床方法，这些方法旨在针对肿瘤缺氧来增强 GBM 对传统疗法的反应，以及它们的结果和临床转化的局限性。© 2024。作者。

Glioblastoma multiforme (GBM) is the most common adult primary brain tumor. The standard clinical treatment of GBM includes a maximal surgical resection followed by concomitant radiotherapy (RT) and chemotherapy sessions with Temozolomide (TMZ) in addition to adjuvant TMZ cycles. Despite the severity of this protocol, GBM is highly resistant and recurs in almost all cases while the protocol remains unchanged since 2005. Limited-diffusion or chronic hypoxia has been identified as one of the major key players driving this aggressive phenotype. The presence of hypoxia within the tumor bulk contributes to the activation of hypoxia signaling pathway mediated by the hypoxia-inducing factors (HIFs), which in turn activate biological mechanisms to ensure the adaptation and survival of GBM under limited oxygen and nutrient supply. Activated downstream pathways are involved in maintaining stem cell-like phenotype, inducing mesenchymal shift, invasion, and migration, altering the cellular and oxygen metabolism, and increasing angiogenesis, autophagy, and immunosuppression. Therefore, in this review will discuss the recent preclinical and clinical approaches that aim at targeting tumor hypoxia to enhance the response of GBM to conventional therapies along with their results and limitations upon clinical translation.© 2024. The Author(s).