The impact of hypoxia and its modification of the outcome of radiotherapy.
The impact of hypoxia and its modification of the outcome of radiotherapy.
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DOI：
10.1093/jrr/rrw007
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发表时间：
2016-08
影响因子：
2
通讯作者：
Overgaard J
中科院分区：
文献类型：
--
作者：
Horsman MR;Overgaard J
自从上个世纪初进行的初步观察以来，已经确定实体瘤包含低氧（缺氧）区域。肿瘤细胞可以在这些低氧条件下存活，并且是肿瘤放射抗性的主要因素。这种重要性导致低氧成为转化放射肿瘤学中引用最多的生物学主题。识别人类肿瘤中的缺氧细胞已变得至关重要，并且通过新的成像技术和使用预测基因谱的帮助，已经提高了这样做的能力。大量的数据证实了在许多类型的人类肿瘤中存在缺氧，尽管个体肿瘤之间存在相当大的异质性。已经研究了用于消除缺氧群体的各种方法。这些措施包括增加氧的可用性，直接放射增敏或杀死缺氧细胞，通过靶向肿瘤血管供应间接影响它们，增加对这种抗性群体的辐射剂量，或通过使用具有高线性能量转移的辐射，缺氧被认为是一个问题。在过去的50年里，这些方法中的许多方法都经历了对照临床试验，结果表明，低氧辐射抗性确实可以克服。因此，存在充足的数据来支持低氧修饰益处的高水平证据。然而，这种低氧修饰仍然对一般临床实践没有影响。在这篇综述中，我们总结了生物学原理，目前的活动和试验，有关识别和克服缺氧在现代放射治疗。
Since the initial observations made at the beginning of the last century, it has been established that solid tumors contain regions of low oxygenation (hypoxia). Tumor cells can survive in these hypoxic conditions and are a major factor in tumor radioresistance. This significance has resulted in hypoxia becoming the most cited biological topic in translational radiation oncology. Identifying hypoxic cells in human tumors has become paramount, and the ability to do this has been improved by the help of new imaging techniques and the use of predictive gene profiles. Substantial data confirm the presence of hypoxia in many types of human tumors, although with considerable heterogeneity among individual tumors. Various approaches have been investigated for eliminating the hypoxic population. These include increasing oxygen availability, directly radiosensitizing or killing the hypoxic cells, indirectly affecting them by targeting the tumor vascular supply, increasing the radiation dose to this resistant population, or by using radiation with a high linear energy transfer, for which hypoxia is believed to be less of an issue. Many of these approaches have undergone controlled clinical trials during the last 50 years, and the results have shown that hypoxic radiation resistance can indeed be overcome. Thus, ample data exists to support a high level of evidence for the benefit of hypoxic modification. However, such hypoxic modification still has no impact on general clinical practice. In this review we summarize the biological rationale, and the current activities and trials, related to identifying and overcoming hypoxia in modern radiotherapy.