Glioblastoma multiforme (GBM) represents a diverse spectrum of primary tumors notorious for their resistance to established therapeutic modalities. Despite aggressive interventions like surgery, radiation, and chemotherapy, these tumors, due to factors such as the blood–brain barrier, tumor heterogeneity, glioma stem cells (GSCs), drug efflux pumps, and DNA damage repair mechanisms, persist beyond complete isolation, resulting in dismal outcomes for glioma patients. Presently, the standard initial approach comprises surgical excision followed by concurrent chemotherapy, where temozolomide (TMZ) serves as the foremost option in managing GBM patients. Subsequent adjuvant chemotherapy follows this regimen. Emerging therapeutic approaches encompass immunotherapy, including checkpoint inhibitors, and targeted treatments, such as bevacizumab, aiming to exploit vulnerabilities within GBM cells. Nevertheless, there exists a pressing imperative to devise innovative strategies for both diagnosing and treating GBM. This review emphasizes the current knowledge of GSC biology, molecular mechanisms, and associations with various signals and/or pathways, such as the epidermal growth factor receptor, PI3K/AKT/mTOR, HGFR/c-MET, NF-κB, Wnt, Notch, and STAT3 pathways. Metabolic reprogramming in GSCs has also been reported with the prominent activation of the glycolytic pathway, comprising aldehyde dehydrogenase family genes. We also discuss potential therapeutic approaches to GSC targets and currently used inhibitors, as well as their mode of action on GSC targets.
多形性胶质母细胞瘤（GBM）代表了一类异质性显著的原发性肿瘤，以其对现有治疗手段的抵抗性而著称。尽管采取了手术、放疗和化疗等积极干预措施，但由于血脑屏障、肿瘤异质性、胶质瘤干细胞（GSCs）、药物外排泵以及DNA损伤修复机制等因素，这些肿瘤难以被完全清除，导致胶质瘤患者预后极差。目前，标准的初始治疗方案包括手术切除联合术后同步放化疗，其中替莫唑胺（TMZ）是治疗GBM患者的首选化疗药物，后续通常辅以辅助化疗。新兴的治疗方法包括免疫疗法（如检查点抑制剂）和靶向治疗（如贝伐珠单抗），旨在利用GBM细胞的脆弱性。然而，开发诊断和治疗GBM的创新策略仍是一项紧迫任务。本综述重点阐述了当前对GSC生物学特性、分子机制及其与多种信号和/或通路（如表皮生长因子受体、PI3K/AKT/mTOR、HGFR/c-MET、NF-κB、Wnt、Notch和STAT3通路）关联的认识。研究还报道了GSC中的代谢重编程，其中糖酵解通路（涉及醛脱氢酶家族基因）的显著激活尤为突出。此外，我们也讨论了针对GSC靶点的潜在治疗策略、目前使用的抑制剂及其对GSC靶点的作用模式。
肿瘤(癌症)患者之家