Laboratory of Neuroscience and Neurogenetics, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, 1000, Bangladesh.
Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, 1000, Bangladesh.
Mol Biol Rep. 2024 Oct 19;51(1):1069. doi: 10.1007/s11033-024-09996-3.
Glioblastoma Multiforme (GBM), designated as grade IV by the World Health Organization, is the most aggressive and challenging brain tumor within the central nervous system. Around 80% of GBM patients have a poor prognosis, with a median survival of 12-15 months. Approximately 90% of GBM cases originate from normal glial cells via oncogenic processes, while the remainder arise from low-grade tumors. GBM is notorious for its heterogeneity, high recurrence rates, invasiveness, and aggressive behavior. Its malignancy is driven by increased invasive migration, proliferation, angiogenesis, and reduced apoptosis. Throughout various stages of central nervous system (CNS) development, pivotal signaling pathways, including Wnt/β-catenin, Sonic hedgehog signaling (Shh), PI3K/AKT/mTOR, Ras/Raf/MAPK/ERK, STAT3, NF-КB, TGF-β, and Notch signaling, orchestrate the growth, proliferation, differentiation, and migration of neural progenitor cells in the brain. Numerous upstream and downstream regulators within these signaling pathways have been identified as significant contributors to the development of human malignancies. Disruptions or aberrant activations in these pathways are linked to gliomagenesis, enhancing the invasiveness, progression, and aggressiveness of GBM, along with epithelial to mesenchymal transition (EMT) and the presence of glioma stem cells (GSCs). Traditional GBM treatment involves surgery, radiotherapy, and chemotherapy with Temozolomide (TMZ). However, most patients experience tumor recurrence, leading to low survival rates. This review provides an overview of the major cell signaling pathways involved in gliomagenesis. Furthermore, we explore the signaling pathways leading to therapy resistance and target key molecules within these signaling pathways, paving the way for the development of novel therapeutic approaches.
多形性胶质母细胞瘤（GBM）被世界卫生组织（WHO）定为 4 级，是中枢神经系统中最具侵袭性和挑战性的脑肿瘤。约 80%的 GBM 患者预后不良，中位生存期为 12-15 个月。约 90%的 GBM 病例源于正常胶质细胞的致癌过程，其余则源于低级别肿瘤。GBM 以异质性高、复发率高、侵袭性强和行为侵袭性强而臭名昭著。其恶性程度是由侵袭性迁移、增殖、血管生成增加和凋亡减少驱动的。在中枢神经系统（CNS）发育的各个阶段，包括 Wnt/β-catenin、Sonic hedgehog 信号（Shh）、PI3K/AKT/mTOR、Ras/Raf/MAPK/ERK、STAT3、NF-КB、TGF-β和 Notch 信号在内的关键信号通路，协调脑内神经祖细胞的生长、增殖、分化和迁移。这些信号通路中的许多上游和下游调节剂已被确定为人类恶性肿瘤发展的重要因素。这些通路中的中断或异常激活与 gliomagenesis 有关，增强了 GBM 的侵袭性、进展性和侵袭性，以及上皮间质转化（EMT）和胶质瘤干细胞（GSCs）的存在。传统的 GBM 治疗包括手术、放疗和替莫唑胺（TMZ）化疗。然而，大多数患者会出现肿瘤复发，导致生存率低。本综述概述了参与 gliomagenesis 的主要细胞信号通路。此外，我们探讨了导致治疗耐药性的信号通路，并针对这些信号通路中的关键分子进行了研究，为开发新的治疗方法铺平了道路。
