Laboratory of Nervous System Diseases and Therapy, GIGA-Neurosciences, University of Liège, Liège, Belgium.
Department of Neurosurgery, CHU and University of Liège, Liège, Belgium.
Target Oncol. 2017 Feb;12(1):11-18. doi: 10.1007/s11523-016-0457-2.
The main obstacle for the cure of glioblastoma (GBM) is systematic tumor recurrence after treatment. More than 90 % of GBM tumors are indeed recurrent within 5 years after diagnosis and treatment. We urgently need new therapies to specifically address these deadly relapses. A major advance in the understanding of GBM recurrence is the identification of GBM-Initiating Cells (GIC), characterized by their abilities for self-renewal, multilineage differentiation, and proliferation. It appears that these features of GIC could be modulated by the mitotic kinase Aurora A (AurA). Indeed, besides its role in mitosis, AurA has recently been identified to regulate alternative functions like cell polarity, asymmetric cell division, and epithelial to mesenchymal transition. All these properties may help explain GBM therapeutic resistance and recurrence. In this review, we make the hypothesis that AurA could significantly contribute to GBM recurrences and we focus on the possible roles of AurA in GIC.
胶质母细胞瘤(GBM)治疗的主要障碍是治疗后系统性肿瘤复发。超过 90%的 GBM 肿瘤在诊断和治疗后 5 年内确实会复发。我们迫切需要新的治疗方法来专门解决这些致命的复发。对 GBM 复发的认识的一个主要进展是鉴定出胶质母细胞瘤起始细胞(GIC),其特征是自我更新、多能分化和增殖能力。看来,GIC 的这些特征可以通过有丝分裂激酶 Aurora A(AurA)来调节。事实上,除了在有丝分裂中的作用外,AurA 最近还被确定可以调节细胞极性、不对称细胞分裂和上皮间质转化等替代功能。所有这些特性都可能有助于解释 GBM 的治疗抵抗和复发。在这篇综述中,我们提出了 AurA 可能对 GBM 复发有重要贡献的假设,并重点介绍了 AurA 在 GIC 中的可能作用。