Overcoming tumor hypoxia as a barrier to radiotherapy, chemotherapy and immunotherapy in cancer treatment.
Overcoming tumor hypoxia as a barrier to radiotherapy, chemotherapy and immunotherapy in cancer treatment.
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DOI：
10.2147/ijn.s140462
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发表时间：
2018
影响因子：
8
通讯作者：
Unger E
中科院分区：
文献类型：
--
作者：
Graham K;Unger E
大多数实体肿瘤都存在一定程度的缺氧，这是由于异常的血管供氧不足，不能满足癌细胞快速增殖的需要。同一肿瘤内的氧合水平在不同区域之间是高度可变的，并且可以随时间而改变。肿瘤缺氧是影响肿瘤有效治疗的重要因素。在放射治疗中，主要机制是产生活性氧；因此，低氧肿瘤具有抗辐射性。许多化疗药物已被证明在暴露于低氧环境时效果较差，这可能导致疾病进一步进展。在癌症治疗中，缺氧也是有效免疫治疗的一个有力障碍。由于认识到缺氧是癌症治疗的一个重要障碍，人们采取了各种方法来克服或逆转肿瘤缺氧。这些方法包括呼吸高压氧、人工血红蛋白、变构血红蛋白调节剂、缺氧激活前药和碳氟化合物（fc）。由于疗效有限和/或不良副作用，这些方法在很大程度上失败了。以液体fc为基础的氧气疗法可以潜在地增加血液的携氧能力，从而逆转肿瘤缺氧。目前，至少有两种药物正在临床试验中，以逆转肿瘤缺氧；其中一种是为了提高氧气进入肿瘤组织的渗透性，另一种是基于低沸点FC，每克FC比以前测试过的FC输送更多的氧气。
Hypoxia exists to some degree in most solid tumors due to inadequate oxygen delivery of the abnormal vasculature which cannot meet the demands of the rapidly proliferating cancer cells. The levels of oxygenation within the same tumor are highly variable from one area to another and can change over time. Tumor hypoxia is an important impediment to effective cancer therapy. In radiotherapy, the primary mechanism is the creation of reactive oxygen species; hypoxic tumors are therefore radiation resistant. A number of chemotherapeutic drugs have been shown to be less effective when exposed to a hypoxic environment which can lead to further disease progression. Hypoxia is also a potent barrier to effective immunotherapy in cancer treatment. Because of the recognition of hypoxia as an important barrier to cancer treatment, a variety of approaches have been undertaken to overcome or reverse tumor hypoxia. Such approaches have included breathing hyperbaric oxygen, artificial hemoglobins, allosteric hemoglobin modifiers, hypoxia activated prodrugs and fluorocarbons (FCs). These approaches have largely failed due to limited efficacy and/or adverse side effects. Oxygen therapeutics, based on liquid FCs, can potentially increase the oxygen-carrying capacity of the blood to reverse tumor hypoxia. Currently, at least two drugs are in clinical trials to reverse tumor hypoxia; one of these is designed to improve permeability of oxygen into the tumor tissue and the other is based upon a low boiling point FC that transports higher amounts of oxygen per gram than previously tested FCs.