Department of Pathology, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA 02115, USA.
Curr Mol Med. 2009 Jun;9(5):580-90. doi: 10.2174/156652409788488739.
Malignant gliomas are the most common primary brain tumors. Despite efforts to find effective treatments, these tumors remain incurable. The failure of malignant gliomas to respond to conventional cancer therapies may reflect the unique biology of these tumors, underscoring the need for new approaches in their investigation. Recently, progress has been made in characterization of the molecular pathogenesis of glioblastoma using a developmental neurobiological perspective, by exploring the role of signaling pathways that control the differentiation of neural stem cells along the glial lineage. The transcription factor STAT3, which has an established function in neural stem cell and astrocyte development, has been found to play dual tumor suppressive and oncogenic roles in glial malignancy depending on the mutational profile of the tumor. These findings establish a novel developmental paradigm in the study of glioblastoma pathogenesis and provide the rationale for patient-tailored therapy in the treatment of this devastating disease.
恶性胶质瘤是最常见的原发性脑肿瘤。尽管人们努力寻找有效的治疗方法，但这些肿瘤仍然无法治愈。恶性胶质瘤对常规癌症治疗的反应不佳，可能反映了这些肿瘤的独特生物学特性，这突显了需要在研究中采用新的方法。最近，人们在使用发育神经生物学观点来描述胶质母细胞瘤的分子发病机制方面取得了进展，探索了控制神经干细胞沿着胶质谱系分化的信号通路的作用。转录因子 STAT3 在神经干细胞和星形胶质细胞发育中具有既定的功能，根据肿瘤的突变情况，在神经胶质恶性肿瘤中发挥双重肿瘤抑制和致癌作用。这些发现为胶质母细胞瘤发病机制的研究建立了一个新的发育范例，并为针对这种破坏性疾病的个体化治疗提供了依据。
