Horsman M R, Sørensen B S, Busk M, Siemann D W
Experimental Clinical Oncology - Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
Experimental Clinical Oncology - Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark.
Clin Oncol (R Coll Radiol). 2021 Nov;33(11):e492-e509. doi: 10.1016/j.clon.2021.08.014. Epub 2021 Sep 14.
Regions of reduced oxygenation (hypoxia) are a characteristic feature of virtually all animal and human solid tumours. Numerous preclinical studies, both in vitro and in vivo, have shown that decreasing oxygen concentration induces resistance to radiation. Importantly, hypoxia in human tumours is a negative indicator of radiotherapy outcome. Hypoxia also contributes to resistance to other cancer therapeutics, including immunotherapy, and increases malignant progression as well as cancer cell dissemination. Consequently, substantial effort has been made to detect hypoxia in human tumours and identify realistic approaches to overcome hypoxia and improve cancer therapy outcomes. Hypoxia-targeting strategies include improving oxygen availability, sensitising hypoxic cells to radiation, preferentially killing these cells, locating the hypoxic regions in tumours and increasing the radiation dose to those areas, or applying high energy transfer radiation, which is less affected by hypoxia. Despite numerous clinical studies with each of these hypoxia-modifying approaches, many of which improved both local tumour control and overall survival, hypoxic modification has not been established in routine clinical practice. Here we review the background and significance of hypoxia, how it can be imaged clinically and focus on the various hypoxia-modifying techniques that have undergone, or are currently in, clinical evaluation.
氧合降低区域（缺氧）实际上是所有动物和人类实体瘤的一个特征。大量的临床前体外和体内研究表明，降低氧浓度会诱导对辐射的抗性。重要的是，人类肿瘤中的缺氧是放疗结果的一个负面指标。缺氧还会导致对包括免疫疗法在内的其他癌症治疗方法产生抗性，并增加恶性进展以及癌细胞扩散。因此，人们付出了巨大努力来检测人类肿瘤中的缺氧情况，并确定克服缺氧和改善癌症治疗结果的切实可行方法。针对缺氧的策略包括提高氧的可利用性、使缺氧细胞对辐射敏感、优先杀死这些细胞、定位肿瘤中的缺氧区域并增加对这些区域的辐射剂量，或应用受缺氧影响较小的高能量转移辐射。尽管对这些缺氧改善方法中的每一种都进行了大量临床研究，其中许多方法都改善了局部肿瘤控制和总生存期，但缺氧改善尚未在常规临床实践中确立。在此，我们综述缺氧的背景和意义、其临床成像方法，并重点关注已进行或目前正在进行临床评估的各种缺氧改善技术。
