Nakano Ichiro, Saya Hideyuki
Department of Neurological Surgery, The Ohio State University, Ohio, USA. Ichiro.Nakano.osumc.edu
No Shinkei Geka. 2010 Oct;38(10):879-89.
Malignant glioma is one of the most lethal diseases in adulthood. The median survival of patients with the Grade IV glioma, glioblastoma multiforme (GBM), is shorter than 15 months and the current first-line therapies for this devastating disease have only a palliative effect. The cancer stem cell hypothesis has recently attracted a great deal of attention, owing to the promise of a novel cellular target for the treatment of tumors including GBM. Recent studies have demonstrated that existence of cancer stem cells in brain tumors (BTSC) accounts, at least in part, for the intractability of malignant glioma. From the therapeutic standpoint, characterization of the mechanism for tumor initiation and maintenance of the "stem-like state" of BTSC is crucial. However, multiple heterogeneous subtypes of cancer stem cells have recently been identified from malignant glioma, making the idea of cancer stem cell complicated. In addition, in some cancer types (e.g. melanoma), a considerable proportion of tumor cells may possess the stem cell property, indicating cancer stem cells may not be a rare cell population in tumors, at least in some organs. Based on the extensive genetic and epigenetic characterization of tumor growth mechanisms, various molecularly-targeted therapies have already been applied for patients, demonstrating a varying degree of success in cancer treatment. A significant improvement in patient prognosis was achieved in several cancer types including leukemia and breast cancer. It is no doubt that continuous effort is required to bring hope for patients with malignant glioma. In this study, we summarize the recent findings and approaches in the cancer stem cell field, mainly focusing on malignant glioma stem cells, and also describe potential future directions in this area.
恶性胶质瘤是成年期最致命的疾病之一。IV级胶质瘤（多形性胶质母细胞瘤，GBM）患者的中位生存期短于15个月，目前针对这种毁灭性疾病的一线治疗仅具有姑息作用。癌症干细胞假说最近引起了广泛关注，因为它有望成为包括GBM在内的肿瘤治疗的新型细胞靶点。最近的研究表明，脑肿瘤中的癌症干细胞（BTSC）的存在至少部分地解释了恶性胶质瘤的难治性。从治疗的角度来看，表征肿瘤起始机制以及BTSC“干细胞样状态”的维持机制至关重要。然而，最近从恶性胶质瘤中鉴定出了多种异质性癌症干细胞亚型，这使得癌症干细胞的概念变得复杂。此外，在某些癌症类型（如黑色素瘤）中，相当一部分肿瘤细胞可能具有干细胞特性，这表明癌症干细胞在肿瘤中可能不是罕见的细胞群体，至少在某些器官中是这样。基于对肿瘤生长机制的广泛遗传和表观遗传特征分析，各种分子靶向疗法已经应用于患者，在癌症治疗中取得了不同程度的成功。包括白血病和乳腺癌在内的几种癌症类型患者的预后有了显著改善。毫无疑问，需要持续努力为恶性胶质瘤患者带来希望。在本研究中，我们总结了癌症干细胞领域的最新发现和方法，主要聚焦于恶性胶质瘤干细胞，并描述了该领域潜在的未来发展方向。
