Despite multimodal therapies, the treatment of glioblastoma remains challenging. In addition to the very complex mechanisms of cancer cells, including specialized phenotypes that enable them to proliferate, invade tissues, and evade immunosurveillance, they exhibit a pronounced resistance to chemo- and radiotherapy. More advanced tumors create a hypoxic environment that supports their proliferation and survival, while robust angiogenesis ensures a constant supply of nutrients. In GBM, these structures are very pronounced and contribute to the creation and maintenance of a highly immunosuppressive microenvironment that promotes tumor growth and immune escape. In addition, the high accumulation of immunosuppressive tumor-infiltrating leukocytes and other cells, the pronounced expression of immune checkpoint molecules, and the low mutational burden, i.e., the low number of neoantigens, are hallmarks of GBM and contribute to the challenge of therapeutic approaches. Here, we review a number of mechanisms that GBM exploits to support tumor growth and potential treatments. These include new chemotherapeutics, tumor treating fields, and small molecules, including compounds targeting angiogenesis or blockers of tyrosine kinases that inhibit tumor cell proliferation and survival. In addition, we focus on immunotherapies such as immune checkpoint blockade or cell therapies, in particular vaccination with dendritic cells and CAR-T cells, which can either kill GBM cells directly or bypass immunosuppression by modulating the tumor microenvironment or boosting the patient’s own immune response.
尽管采用多模式疗法，胶质母细胞瘤的治疗仍面临挑战。除了癌细胞自身复杂的机制——包括使其能够增殖、侵袭组织并逃避免疫监视的特化表型外，它们对化疗和放疗表现出显著的抵抗性。更晚期的肿瘤会形成支持其增殖和存活的缺氧环境，而活跃的血管生成则确保营养的持续供应。在胶质母细胞瘤中，这些结构尤为突出，共同形成并维持高度免疫抑制的微环境，从而促进肿瘤生长和免疫逃逸。此外，免疫抑制性肿瘤浸润白细胞及其他细胞的高度聚集、免疫检查点分子的显著表达以及低突变负荷（即新抗原数量稀少）是胶质母细胞瘤的典型特征，这些因素共同增加了治疗难度。本文综述了胶质母细胞瘤利用以支持肿瘤生长的多种机制及潜在治疗方法，包括新型化疗药物、肿瘤治疗电场以及靶向血管生成的小分子化合物或抑制肿瘤细胞增殖存活的酪氨酸激酶阻断剂。同时，我们重点关注免疫疗法，如免疫检查点阻断或细胞疗法，特别是树突状细胞疫苗和CAR-T细胞疗法，这些疗法可直接杀伤胶质母细胞瘤细胞，或通过调节肿瘤微环境、增强患者自身免疫反应来克服免疫抑制。
肿瘤(癌症)患者之家