a OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf , Dresden , Germany.
b National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz-Zentrum Dresden - Rossendorf (HZDR) , Dresden , Germany.
Int J Radiat Biol. 2019 Jul;95(7):900-911. doi: 10.1080/09553002.2019.1589023. Epub 2019 Mar 29.
Despite technological improvement and advances in biology-driven patient stratification, many patients still fail radiotherapy resulting in loco-regional and distant recurrence. Tumor heterogeneity remains a key challenge to effective cancer treatment, and reliable stratification of cancer patients for prediction of outcomes is highly important. Intratumoral heterogeneity is manifested at the different levels, including different tumorigenic properties of cancer cells. Since John Dick et al. isolated leukemia initiating cells in 1990, the populations of tumor initiating or cancer stem cells (CSCs) were identified and characterized also for a broad spectrum of solid tumor types. The properties of CSCs are of considerable clinical relevance: CSCs have self-renewal and tumor initiating potential, and the metastases are initiated by the CSC clones with the ability to disseminate from the primary tumor site. Evidence from both, experimental and clinical studies demonstrates that the probability of achieving local tumor control by radiation therapy depends on the complete eradication of CSC populations. The number, properties and molecular signature of CSCs are highly predictive for clinical outcome of radiotherapy, whereas targeted therapies against CSCs combined with conventional treatment are expected to provide an improved clinical response and prevent tumor relapse. In this review, we discuss the modern methods to study CSCs in radiation biology, the role of CSCs in personalized cancer therapy as well as future directions for CSC research in translational radiooncology.
尽管技术不断进步，生物学驱动的患者分层也取得了进展，但仍有许多患者的放疗失败，导致局部和远处复发。肿瘤异质性仍然是癌症治疗的一个关键挑战，对癌症患者进行可靠的分层以预测治疗结果非常重要。肿瘤内异质性表现在不同的水平上，包括癌细胞的不同肿瘤发生特性。自 John Dick 等人于 1990 年分离出白血病起始细胞以来，肿瘤起始或癌症干细胞 (CSC) 的群体也已被鉴定和表征，广泛涉及多种实体肿瘤类型。CSC 的特性具有重要的临床意义：CSC 具有自我更新和肿瘤起始能力，转移是由具有从原发肿瘤部位扩散能力的 CSC 克隆引发的。实验和临床研究都证明，通过放射治疗实现局部肿瘤控制的概率取决于 CSC 群体的完全根除。CSC 的数量、特性和分子特征对放射治疗的临床结果具有高度预测性，而针对 CSC 的靶向治疗与常规治疗相结合有望提供更好的临床反应并防止肿瘤复发。在这篇综述中，我们讨论了放射生物学中研究 CSC 的现代方法、CSC 在个体化癌症治疗中的作用以及转化放射肿瘤学中 CSC 研究的未来方向。
