How Can We Overcome Tumor Hypoxia in Radiation Therapy?
How Can We Overcome Tumor Hypoxia in Radiation Therapy?
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DOI：
10.1269/jrr.11056
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发表时间：
2011-09-01
影响因子：
2
通讯作者：
Harada, Hiroshi
中科院分区：
文献类型：
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作者：
Harada, Hiroshi
局部复发和远处转移经常发生在癌症放射治疗后，可能是致命的。从放射化学和放射生物学研究中获得的证据表明，这些问题至少部分是由肿瘤特异性微环境缺氧引起的。此外，一个转录因子，缺氧诱导因子1（HIF-1），被确定为关键的缺氧介导的辐射抗性。为了克服这些问题，放射肿瘤学家最近获得了强有力的工具，如“同时整合增强调强放射治疗（SIB-IMRT），其使得能够将增强剂量的辐射递送到恶性肿瘤中的小目标部分”、“低氧选择性细胞毒素/药物”和“HIF-1抑制剂”等。为了充分利用这些创新的和跨学科的癌症治疗策略，揭示肿瘤生长期间和放射治疗后低氧/HIF-1活性肿瘤细胞的特征、肿瘤内定位和动力学是至关重要的。我们已经使用荷瘤小鼠进行了光学成像实验，并发现随着肿瘤的生长，HIF-1活性肿瘤细胞的位置发生了显着变化。此外，HIF-1活性在放射治疗后显著变化。本文综述了目前放射治疗中肿瘤乏氧的基本问题，HIF-1在肿瘤放射抵抗中的作用，乏氧肿瘤细胞在肿瘤生长过程中和放射治疗后的动力学，以及如何利用创新的跨学科技术克服放射治疗的困难。
Local recurrence and distant metastasis frequently occur after radiation therapy for cancer and can be fatal. Evidence obtained from radiochemical and radiobiological studies has revealed these problems to be caused, at least in part, by a tumor-specific microenvironment, hypoxia. Moreover, a transcription factor, hypoxia-inducible factor 1 (HIF-1), was identified as pivotal to hypoxia-mediated radioresistance. To overcome the problems, radiation oncologists have recently obtained powerful tools, such as "simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT), which enables a booster dose of radiation to be delivered to small target fractions in a malignant tumor", "hypoxia-selective cytotoxins/drugs", and "HIF-1 inhibitors" etc. In order to fully exploit these innovative and interdisciplinary strategies in cancer therapy, it is critical to unveil the characteristics, intratumoral localization, and dynamics of hypoxia/HIF-1-active tumor cells during tumor growth and after radiation therapy. We have performed optical imaging experiments using tumor-bearing mice and revealed that the locations of HIF-1-active tumor cells changes dramatically as tumors grow. Moreover, HIF-1 activity changes markedly after radiation therapy. This review overviews 1) fundamental problems surrounding tumor hypoxia in current radiation therapy, 2) the function of HIF-1 in tumor radioresistance, 3) the dynamics of hypoxic tumor cells during tumor growth and after radiation therapy, and 4) how we should overcome the difficulties with radiation therapy using innovative interdisciplinary technologies.