Targeting Hypoxia, HIF-1, and Tumor Glucose Metabolism to Improve Radiotherapy Efficacy
Targeting Hypoxia, HIF-1, and Tumor Glucose Metabolism to Improve Radiotherapy Efficacy
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DOI：
10.1158/1078-0432.ccr-12-0858
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发表时间：
2012-10-15
影响因子：
11.5
通讯作者：
Bussink, Johan
中科院分区：
文献类型：
--
作者：
Meijer, Tineke W. H.;Kaanders, Johannes H. A. M.;Bussink, Johan
放射治疗是一种重要的肿瘤治疗方式，通过诱导氧化应激杀死细胞。然而，恶性肿瘤对辐照的反应各不相同，这是发生在分子水平上的耐药机制的结果。了解这些放射耐药机制是很重要的，因为抵消它们可能会提高放射治疗的疗效。在这篇综述中，我们描述了缺氧诱导因子1 （HIF-1）途径如何对放疗反应产生深远影响。主要的焦点将是HIF-1控制的辐射后血管保护，以及HIF-1对糖酵解和戊糖磷酸途径的调节。这种异常的细胞代谢增加了肿瘤的抗氧化能力，从而对抗照射引起的氧化应激。从转化研究和首批临床I/II期试验的结果可以得出，在多个水平上靶向HIF-1和肿瘤糖代谢会降低肿瘤的抗氧化能力，影响肿瘤微环境，并使多种实体肿瘤对辐照致敏。临床癌症研究；18 (20);5585 - 94。(c) 2012年aacr。
Radiotherapy, an important treatment modality in oncology, kills cells through induction of oxidative stress. However, malignant tumors vary in their response to irradiation as a consequence of resistance mechanisms taking place at the molecular level. It is important to understand these mechanisms of radioresistance, as counteracting them may improve the efficacy of radiotherapy. In this review, we describe how the hypoxia-inducible factor 1 (HIF-1) pathway has a profound effect on the response to radiotherapy. The main focus will be on HIF-1-controlled protection of the vasculature postirradiation and on HIF-1 regulation of glycolysis and the pentose phosphate pathway. This aberrant cellular metabolism increases the antioxidant capacity of tumors, thereby countering the oxidative stress caused by irradiation. From the results of translational studies and the first clinical phase I/II trials, it can be concluded that targeting HIF-1 and tumor glucose metabolism at several levels reduces the antioxidant capacity of tumors, affects the tumor microenvironment, and sensitizes various solid tumors to irradiation. Clin Cancer Res; 18(20); 5585-94. (C) 2012 AACR.