Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Semin Cancer Biol. 2010 Apr;20(2):116-24. doi: 10.1016/j.semcancer.2010.02.003. Epub 2010 Feb 26.
Despite continuous improvements in cancer management, locoregional recurrence or metastatic spread still occurs in a high proportion of patients after radiotherapy or combined treatments. One underlying reason might be a low efficacy of current treatments on eradication of cancer stem cells (CSCs). It has been recognised for a long time, that only the small subpopulation of CSCs can cause recurrences and that all CSCs need to be killed for permanent tumour cure. However, only recently novel technologies have allowed to enrich CSCs and to investigate their biology. An emerging experimental and clinical database provides first hints that cell populations accumulated by putative stem cell markers or tumours that highly express such markers may be more radioresistant than their marker-negative counterparts. Other data support a higher tolerance of CSCs to hypoxia and preferential location in specific microenvironmental niches. However, conflicting data, methodological problems of the assays and a generally small database on only few tumour types necessitate further large and well-designed prospective experimental and clinical investigations that specifically address this question to corroborate this hypothesis. If such investigations confirm biological differences between CSCs and non-CSCs, this would imply that novel treatment strategies need to be tested specifically for their effect on CSCs. Another implication is that also biomarkers for prediction of local tumour control after radiotherapy or combined treatments need to reflect the behaviour of CSCs and not of the bulk of all cancer cells. This review discusses the importance of CSCs for treatment failure and challenges occurring from the CSC concept for cancer diagnosis, treatment and prediction of outcome. It is concluded that CSC-based endpoints and biomarkers are eventually expected to considerably improve tumour cure rates in the clinics through individualised tailoring of treatment.
尽管癌症治疗不断取得进展，但放疗或联合治疗后，仍有很大一部分患者发生局部区域复发或转移扩散。一个潜在的原因可能是当前治疗方法在消除癌症干细胞 (CSC) 方面的效果不佳。长期以来，人们已经认识到，只有一小部分 CSC 能够引起复发，只有杀死所有的 CSCs 才能实现肿瘤的永久治愈。然而，直到最近，新技术才允许富集 CSC 并研究其生物学特性。一个新兴的实验和临床数据库提供了初步线索，表明通过假定的干细胞标志物或高度表达这些标志物的肿瘤积累的细胞群体可能比其标志物阴性的对应物具有更强的抗辐射能力。其他数据支持 CSC 对缺氧的耐受性更高，并优先位于特定的微环境龛位。然而，相互矛盾的数据、检测方法的方法学问题以及仅针对少数肿瘤类型的数据库通常较小，这需要进一步进行大规模、精心设计的前瞻性实验和临床研究，以专门针对这一问题来验证这一假设。如果这些研究证实了 CSC 和非 CSC 之间存在生物学差异，这将意味着需要针对 CSC 来测试新的治疗策略。另一个含义是，预测放疗或联合治疗后局部肿瘤控制的生物标志物也需要反映 CSC 的行为，而不是所有癌细胞的总体行为。这篇综述讨论了 CSC 对治疗失败的重要性，以及 CSC 概念对癌症诊断、治疗和预后预测所带来的挑战。结论是，基于 CSC 的终点和生物标志物最终有望通过个体化治疗来显著提高临床肿瘤治愈率。
