At the Crossroads of Cancer Stem Cells, Radiation Biology, and Radiation Oncology.
At the Crossroads of Cancer Stem Cells, Radiation Biology, and Radiation Oncology.
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DOI：
10.1158/0008-5472.can-15-2455
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发表时间：
2016-03-01
期刊：
影响因子：
11.2
通讯作者：
Wakimoto H
中科院分区：
文献类型：
--
作者：
Gerweck LE;Wakimoto H
有报道称，一小部分肿瘤细胞启动并维持肿瘤生长，对辐射和药物具有抗性，并携带特定标记，导致癌症干细胞研究激增。这些报告表明，通过肿瘤体积变化评价治疗反应具有误导性，因为体积变化反映的是敏感性而非耐药致瘤细胞群的反应。这些报告进一步表明，基于标记物的肿瘤细胞群体的选择将促进放射治疗方案、敏化剂和药物的开发，所述放射治疗方案、敏化剂和药物特异性靶向导致治疗失败的耐药致瘤细胞。这篇综述提出了证据，质疑的意见，癌症干细胞标志物可靠地识别肿瘤细胞的子集，维持肿瘤生长，和标志物识别的人口是放射性相对于标志物阴性细胞。实验研究表明，在大辐射剂量下存活的细胞和肿瘤并不比未受辐射的细胞和肿瘤更具辐射抗性，并且还表明，未分选的集落形成肿瘤细胞的固有辐射敏感性与肿瘤起始的未分选肿瘤细胞的分数相结合，预测了肿瘤的辐射可治愈性。
Reports that a small subset of tumor cells initiate and sustain tumor growth, are resistant to radiation and drugs, and bear specific markers, have lead to an explosion of cancer stem cell research. These reports imply that the evaluation of therapeutic response by changes in tumor volume is misleading, as volume changes reflects the response of the sensitive rather than the resistant tumorgenic cell population. The reports further suggest that the marker based selection of the tumor cell population will facilitate the development of radiation treatment schedules, sensitizers and drugs which specifically target the resistant tumorgenic cells that give rise to treatment failure. This review presents evidence that contests the observations that cancer stem cell markers reliably identify the subset of tumor cells which sustain tumor growth, and that the marker identified population is radioresistant relative to the marker-negative cells. Experimental studies show that cells and tumors that survive large radiation doses are not more radioresistant than unirradiated cells and tumors, and also show that the intrinsic radiosensitivity of unsorted colony forming tumor cells, in combination with the fraction of unsorted tumor cells that are tumor initiating, predicts tumor radiocurability.