Ramar Vanajothi, Guo Shanchun, Hudson BreAnna, Liu Mingli
Department of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Department of Chemistry, Xavier University, 1 Drexel Dr., New Orleans, LA 70125, USA.
Cancers (Basel). 2023 Dec 24;16(1):102. doi: 10.3390/cancers16010102.
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）是一种多样的原发性肿瘤，以对现有治疗方式具有抗性而臭名昭著。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）、药物外排泵和DNA损伤修复机制等因素，这些肿瘤在完全切除后仍会持续存在，导致胶质瘤患者预后不佳。目前，标准的初始治疗方法包括手术切除，随后进行同步化疗，其中替莫唑胺（TMZ）是治疗GBM患者的首要选择。后续进行辅助化疗。新兴的治疗方法包括免疫疗法，如检查点抑制剂，以及靶向治疗，如贝伐单抗，旨在利用GBM细胞中的弱点。然而，迫切需要设计出诊断和治疗GBM的创新策略。本综述强调了目前对GSC生物学、分子机制以及与各种信号和/或途径（如表皮生长因子受体、PI3K/AKT/mTOR、HGFR/c-MET、NF-κB、Wnt、Notch和STAT3途径）的关联的认识。也有报道称GSCs中的代谢重编程伴随着糖酵解途径的显著激活，包括醛脱氢酶家族基因。我们还讨论了针对GSC靶点的潜在治疗方法和目前使用的抑制剂，以及它们对GSC靶点的作用方式。
