Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Case Comprehensive Cancer Center, Cleveland, Ohio, USA.
Neuro Oncol. 2024 May 3;26(5):785-795. doi: 10.1093/neuonc/noae011.
Over the past 2 decades, the cancer stem cell (CSC) hypothesis has provided insight into many malignant tumors, including glioblastoma (GBM). Cancer stem cells have been identified in patient-derived tumors and in some mouse models, allowing for a deeper understanding of cellular and molecular mechanisms underlying GBM growth and therapeutic resistance. The CSC hypothesis has been the cornerstone of cellular heterogeneity, providing a conceptual and technical framework to explain this longstanding phenotype in GBM. This hypothesis has evolved to fit recent insights into how cellular plasticity drives tumor growth to suggest that CSCs do not represent a distinct population but rather a cellular state with substantial plasticity that can be achieved by non-CSCs under specific conditions. This has further been reinforced by advances in genomics, including single-cell approaches, that have used the CSC hypothesis to identify multiple putative CSC states with unique properties, including specific developmental and metabolic programs. In this review, we provide a historical perspective on the CSC hypothesis and its recent evolution, with a focus on key functional phenotypes, and provide an update on the definition for its use in future genomic studies.
在过去的 20 年中，癌症干细胞（CSC）假说为包括胶质母细胞瘤（GBM）在内的许多恶性肿瘤提供了深入的了解。已经在患者来源的肿瘤和一些小鼠模型中鉴定出了癌症干细胞，从而可以更深入地了解 GBM 生长和治疗耐药性的细胞和分子机制。CSC 假说一直是细胞异质性的基石，为解释 GBM 中这种长期存在的表型提供了一个概念和技术框架。随着最近对细胞可塑性如何驱动肿瘤生长的深入了解，这一假说已经发展到认为 CSC 并不代表一个独特的群体，而是一种具有很大可塑性的细胞状态，非 CSC 在特定条件下可以实现这种状态。这一观点进一步得到了基因组学进展的支持，包括单细胞方法，这些方法利用 CSC 假说来识别具有独特特性的多个潜在 CSC 状态，包括特定的发育和代谢程序。在这篇综述中，我们提供了 CSC 假说及其最近的演变的历史视角，重点介绍了关键的功能表型，并就其在未来基因组研究中的应用定义提供了最新信息。
