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首页> 外文期刊>Seminars in cancer biology >Cancer stem cells at the crossroads of current cancer therapy failures--radiation oncology perspective.
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Cancer stem cells at the crossroads of current cancer therapy failures--radiation oncology perspective.

机译：癌症干细胞正处于当前癌症治疗失败的十字路口-放射肿瘤学的观点。

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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.
机译：尽管在癌症管理方面不断改善，但放疗或联合治疗后仍有很大一部分患者发生局部复发或转移扩散。一个潜在的原因可能是当前疗法在根除癌症干细胞（CSC）方面的功效很低。长期以来，人们已经认识到，只有少量的CSCs可以引起复发，并且需要杀死所有CSCs才能永久治愈肿瘤。但是，只有最近的新技术才允许丰富CSC并研究其生物学。新兴的实验和临床数据库提供了第一个提示，即由推定的干细胞标志物或高度表达此类标志物的肿瘤积累的细胞群可能比其标志物阴性的标本更具放射性。其他数据支持CSC对缺氧和特定微环境生态位中优先位置的较高耐受性。但是，冲突的数据，化验的方法学问题以及仅针对几种肿瘤类型的小型数据库通常需要进行进一步的大型且设计良好的前瞻性实验和临床研究，以专门解决该问题以证实这一假设。如果此类研究证实了CSC和非CSC之间的生物学差异，则意味着需要针对其对CSC的效果进行专门测试新的治疗策略。另一个含义是，用于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大部分。这篇综述讨论了CSC对治疗失败的重要性以及CSC概念在癌症诊断，治疗和预后方面的挑战。结论是，基于CSC的终点和生物标记物最终有望通过个性化的治疗方案在临床上显着提高肿瘤治愈率。

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