Department of Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, University Hospital, Dresden, Germany.
Clin Cancer Res. 2011 Dec 1;17(23):7224-9. doi: 10.1158/1078-0432.CCR-10-2639. Epub 2011 Oct 5.
Cancer stem cells (CSC) have the unique ability to cause tumor recurrences if they survive treatment. Radiotherapy has curative potential because it has been functionally shown to sufficiently inactivate CSCs. It is well known that CSCs mediate the radiation resistance of tumors by tumor-specific factors, such as the pretreatment number of CSCs and repopulation or reoxygenation during fractionated radiotherapy. CSCs appear to have a higher intrinsic radioresistance than non-CSCs, a factor that is especially important for the development of predictive biomarkers that, if this finding holds true, can only be successfully established if they are stem-cell specific. Recent clinical data imply that stem-cell-related surface markers may be directly used as predictors for the radiocurability of tumors with comparable risk factors, such as histology and size. Future studies need to address the question of which additional markers need to be considered if more heterogeneous patient collectives are investigated. With the goal of developing a direct targeting approach, investigators are currently evaluating several drugs that are intended to target CSCs by inhibiting stem-cell-related signal transduction pathways. We need to preclinically test such drugs as combined-modality therapies in combination with radiotherapy to evaluate their curative potential, and optimize them by increasing their specificity to CSCs over normal tissue stem cells to avoid increased radiation toxicity.
癌症干细胞（CSC）如果在治疗后存活下来，就有独特的能力导致肿瘤复发。放射治疗具有治愈的潜力，因为已经证明它能够充分使 CSC 失活。众所周知，CSC 通过肿瘤特异性因子介导肿瘤的辐射抗性，例如 CSC 的预处理数量以及在分次放射治疗期间的再增殖或再氧合。CSC 似乎比非 CSC 具有更高的内在放射抗性，这一因素对于开发预测性生物标志物尤其重要，如果这一发现成立，那么只有在它们是干细胞特异性的情况下才能成功建立。最近的临床数据表明，干细胞相关的表面标志物可以直接用作具有类似危险因素（如组织学和大小）的肿瘤的放射可治愈性的预测因子。未来的研究需要解决在研究更多异质患者群体时需要考虑哪些其他标志物的问题。为了开发直接靶向方法，研究人员目前正在评估几种旨在通过抑制干细胞相关信号转导途径来靶向 CSC 的药物。我们需要在临床前阶段将这些药物作为联合治疗与放射治疗相结合进行测试，以评估其治愈潜力，并通过增加其对 CSC 的特异性来优化它们，以避免增加正常组织干细胞的放射毒性。
