The Glioblastoma Landscape: Hallmarks of Disease, Therapeutic Resistance, and Treatment Opportunities.
The Glioblastoma Landscape: Hallmarks of Disease, Therapeutic Resistance, and Treatment Opportunities.
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DOI：
10.18103/mra.v11i6.3994
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发表时间：
2023-06-30
期刊：
影响因子：
--
通讯作者：
Kelly, Deborah F
中科院分区：
文献类型：
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作者：
Boylan, Jack;Byers, Elizabeth;Kelly, Deborah F
恶性脑肿瘤具有侵袭性，难以治疗。胶质母细胞瘤是原发性脑肿瘤中最常见和最致命的形式，通常在没有遗传易感性的患者中发现。被诊断患有这种疾病的人的平均预期寿命为6个月至2年，目前尚无治愈方法。癌症生物学的新范式暗示了一小部分肿瘤细胞在启动和维持这些无法治愈的脑肿瘤。在这里，我们讨论胶质母细胞瘤的异质性及其治疗抵抗和复发能力背后的理论。在癌症领域，癌症干细胞被认为是肿瘤的启动者，也是肿瘤异质性和治疗逃避的主要贡献者，这种细胞已在胶质母细胞瘤中被发现。在细胞水平上，分化和自我更新之间微妙平衡的破坏刺激转化并支持肿瘤生长。虽然快速分裂的细胞对传统治疗的消除更为敏感，但胶质母细胞瘤干细胞通过缓慢分裂和可逆退出细胞周期来逃避这些措施。在分子水平上，胶质母细胞瘤肿瘤细胞利用几种信号通路，通过改善DNA修复机制和灵活的衰老状态来逃避常规治疗。我们研究了这些常见的逃避技术，同时讨论了潜在的分子方法来更好地靶向这些致命的肿瘤。同样重要的是，这些信息鼓励了用新型胶质母细胞瘤干细胞导向疗法来增强常规治疗的想法，因为消除这些有害的祖细胞具有调节肿瘤复发的巨大潜力。
Malignant brain tumors are aggressive and difficult to treat. Glioblastoma is the most common and lethal form of primary brain tumor, often found in patients with no genetic predisposition. The median life expectancy for individuals diagnosed with this condition is 6 months to 2 years and there is no known cure. New paradigms in cancer biology implicate a small subset of tumor cells in initiating and sustaining these incurable brain tumors. Here, we discuss the heterogenous nature of glioblastoma and theories behind its capacity for therapy resistance and recurrence. Within the cancer landscape, cancer stem cells are thought to be both tumor initiators and major contributors to tumor heterogeneity and therapy evasion and such cells have been identified in glioblastoma. At the cellular level, disruptions in the delicate balance between differentiation and self-renewal spur transformation and support tumor growth. While rapidly dividing cells are more sensitive to elimination by traditional treatments, glioblastoma stem cells evade these measures through slow division and reversible exit from the cell cycle. At the molecular level, glioblastoma tumor cells exploit several signaling pathways to evade conventional therapies through improved DNA repair mechanisms and a flexible state of senescence. We examine these common evasion techniques while discussing potential molecular approaches to better target these deadly tumors. Equally important, the presented information encourages the idea of augmenting conventional treatments with novel glioblastoma stem cell-directed therapies, as eliminating these harmful progenitors holds great potential to modulate tumor recurrence.