Targeting tumor perfusion and oxygenation to improve the outcome of anticancer therapy.
Targeting tumor perfusion and oxygenation to improve the outcome of anticancer therapy.
复制标题
DOI：
10.3389/fphar.2012.00094
复制
发表时间：
2012
影响因子：
5.6
通讯作者：
Sonveaux P
中科院分区：
文献类型：
--
作者：
Jordan BF;Sonveaux P
放射疗法和化学疗法是癌症治疗的广泛临床模式。在其他生物学影响中，缺氧是限制放射治疗功效的主要因素，主要是因为氧参与电离辐射引起的DNA损伤的稳定。在啮齿动物和人类肿瘤区域发现放射性缺氧，组织氧合水平低于10 mmHg，在此水平下肿瘤细胞对辐射损伤的抵抗力越来越强。由于低氧肿瘤细胞保持克隆形成，它们对治疗的抗性强烈影响放射治疗的治疗结果。因此，迫切需要确定旨在增加肿瘤pO2在放疗时的辅助治疗方式。由于肿瘤缺氧从根本上是由效率低下的血管的氧气输送和具有高代谢活性的肿瘤细胞的氧气消耗之间的不平衡引起的，两种有希望的方法是靶向血管反应性和肿瘤细胞呼吸的那些。本文综述了肿瘤选择性血管扩张剂、肿瘤细胞呼吸抑制剂以及结合这两种活性的药物和治疗方法在肿瘤对X射线放射治疗敏感性方面的发展和应用。肿瘤选择性血管舒张也可用于改善循环抗癌剂向肿瘤的递送。肿瘤灌注和氧合成像不仅对于开发和验证此类联合治疗非常重要，而且对于确定哪些患者可以从治疗中受益也非常重要。在临床前环境中已经开发了许多技术。因此，本文还简要介绍了磁共振和非磁共振在体内的方法，并比较它们的灵敏度，定量或半定量性能，时间和空间分辨率，以及平移方面。
Radiotherapy and chemotherapy are widespread clinical modalities for cancer treatment. Among other biological influences, hypoxia is a main factor limiting the efficacy of radiotherapy, primarily because oxygen is involved in the stabilization of the DNA damage caused by ionizing radiations. Radiobiological hypoxia is found in regions of rodent and human tumors with a tissue oxygenation level below 10 mmHg at which tumor cells become increasingly resistant to radiation damage. Since hypoxic tumor cells remain clonogenic, their resistance to the treatment strongly influences the therapeutic outcome of radiotherapy. There is therefore an urgent need to identify adjuvant treatment modalities aimed to increase tumor pO2 at the time of radiotherapy. Since tumor hypoxia fundamentally results from an imbalance between oxygen delivery by poorly efficient blood vessels and oxygen consumption by tumor cells with high metabolic activities, two promising approaches are those targeting vascular reactivity and tumor cell respiration. This review summarizes the current knowledge about the development and use of tumor-selective vasodilators, inhibitors of tumor cell respiration, and drugs and treatments combining both activities in the context of tumor sensitization to X-ray radiotherapy. Tumor-selective vasodilation may also be used to improve the delivery of circulating anticancer agents to tumors. Imaging tumor perfusion and oxygenation is of importance not only for the development and validation of such combination treatments, but also to determine which patients could benefit from the therapy. Numerous techniques have been developed in the preclinical setting. Hence, this review also briefly describes both magnetic resonance and non-magnetic resonance in vivo methods and compares them in terms of sensitivity, quantitative or semi-quantitative properties, temporal, and spatial resolutions, as well as translational aspects.
登录
查看更多内容
影响因子：
8.8
作者：
Dewhirst, MW;Ong, ET;Braun, RD;Smith, B;Klitzman, B;Evans, SM;Wilson, D
通讯作者：
Wilson, D
DOI：
10.1073/pnas.74.8.3203
发表时间：
1977-01-01
影响因子：
11.1
作者：
ARNOLD, WP;MITTAL, CK;MURAD, F
通讯作者：
MURAD, F
影响因子：
11.5
作者：
Frerart, Francoise;Sonveaux, Pierre;Feron, Olivier
通讯作者：
Feron, Olivier
影响因子：
6.2
作者：
Cristofanilli, M;Yamamura, Y;Hortobagyi, GN
通讯作者：
Hortobagyi, GN
DOI：
10.1073/pnas.0600942103
发表时间：
2006-05-30
影响因子：
11.1
作者：
Angelo, Michael;Singel, David J.;Stamler, Jonathan S.
通讯作者：
Stamler, Jonathan S.