Glioblastoma ranks among the most lethal of all human cancers. Glioblastomas display striking cellular heterogeneity, with stem-like glioblastoma stem cells (GSCs) at the apex. Although the original identification of GSCs dates back more than a decade, the purification and characterization of GSCs remains challenging. Despite these challenges, the evidence that GSCs play important roles in tumor growth and response to therapy has grown. Like normal stem cells, GSCs are functionally defined and distinguished from their differentiated tumor progeny at core transcriptional, epigenetic, and metabolic regulatory levels, suggesting that no single therapeutic modality will be universally effective against a heterogenous GSC population. Glioblastomas induce a systemic immunosuppression with mixed responses to oncoimmunologic modalities, suggesting the potential for augmentation of response with a deeper consideration of GSCs. Unfortunately, the GSC literature has been complicated by frequent use of inferior cell lines and a lack of proper functional analyses. Collectively, glioblastoma offers a reliable cancer to study cancer stem cells to better model the human disease and inform improved biologic understanding and design of novel therapeutics.

中文翻译：

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胶质母细胞瘤干细胞：致命癌症中肿瘤等级的教训。

胶质母细胞瘤是所有人类癌症中最致命的癌症之一。胶质母细胞瘤显示出惊人的细胞异质性，在顶端有干细胞样胶质母细胞瘤干细胞 (GSC)。尽管 GSC 的最初鉴定可以追溯到十多年前，但 GSC 的纯化和表征仍然具有挑战性。尽管存在这些挑战，但越来越多的证据表明 GSC 在肿瘤生长和对治疗的反应中发挥重要作用。与正常干细胞一样，GSC 在核心转录、表观遗传和代谢调节水平上的功能定义和区别于它们分化的肿瘤后代，表明没有一种单一的治疗方式对异质 GSC 群体普遍有效。胶质母细胞瘤诱导全身免疫抑制，对肿瘤免疫学方式有混合反应，表明通过更深入地考虑 GSC 可以增强响应。不幸的是，GSC 文献因频繁使用劣质细胞系和缺乏适当的功能分析而变得复杂。总的来说，胶质母细胞瘤提供了一种可靠的癌症来研究癌症干细胞，以更好地模拟人类疾病，并为改进生物学理解和设计新疗法提供信息。