The hypoxic tumour is a chaotic landscape of struggle and adaption. Against the adversity of oxygen starvation, hypoxic cancer cells initiate a reprogramming of transcriptional activities, allowing for survival, metastasis and treatment failure. This makes hypoxia a crucial feature of aggressive tumours. Its importance, to cancer and other diseases, was recognised by the award of the 2019 Nobel Prize in Physiology or Medicine for research contributing to our understanding of the cellular response to oxygen deprivation. For cancers with limited treatment options, for example those that rely heavily on radiotherapy, the results of hypoxic adaption are particularly restrictive to treatment success. A fundamental aspect of this hypoxic reprogramming with direct relevance to radioresistance, is the alteration to the DNA damage response, a complex set of intermingling processes that guide the cell (for good or for bad) towards DNA repair or cell death. These alterations, compounded by the fact that oxygen is required to induce damage to DNA during radiotherapy, means that hypoxia represents a persistent obstacle in the treatment of many solid tumours. Considerable research has been done to reverse, correct or diminish hypoxia’s power over successful treatment. Though many clinical trials have been performed or are ongoing, particularly in the context of imaging studies and biomarker discovery, this research has yet to inform clinical practice. Indeed, the only hypoxia intervention incorporated into standard of care is the use of the hypoxia-activated prodrug Nimorazole, for head and neck cancer patients in Denmark. Decades of research have allowed us to build a picture of the shift in the DNA repair capabilities of hypoxic cancer cells. A literature consensus tells us that key signal transducers of this response are upregulated, where repair proteins are downregulated. However, a complete understanding of how these alterations lead to radioresistance is yet to come.

缺氧肿瘤是一幅挣扎与适应的混乱景象。面对缺氧的逆境，缺氧的癌细胞会启动转录活动的重新编程，从而实现生存、转移和治疗失败。这使得缺氧成为侵袭性肿瘤的一个重要特征。它对癌症和其他疾病的重要性得到了 2019 年诺贝尔生理学或医学奖的认可，以表彰其研究有助于我们了解细胞对缺氧的反应。对于治疗选择有限的癌症，例如那些严重依赖放射治疗的癌症，低氧适应的结果尤其限制治疗的成功。这种与放射抗性直接相关的缺氧重编程的一个基本方面是 DNA 损伤反应的改变，这是一组复杂的混合过程，引导细胞（无论好坏）进行 DNA 修复或细胞死亡。这些变化，再加上放疗期间需要氧气来诱导 DNA 损伤的事实，意味着缺氧是许多实体瘤治疗中的持续障碍。为了扭转、纠正或减少缺氧对成功治疗的影响，已经进行了大量的研究。尽管许多临床试验已经进行或正在进行，特别是在成像研究和生物标志物发现的背景下，但这项研究尚未为临床实践提供信息。事实上，唯一纳入护理标准的缺氧干预措施是对丹麦的头颈癌患者使用缺氧激活的前药尼莫拉唑。数十年的研究使我们能够了解缺氧癌细胞 DNA 修复能力的变化。文献共识告诉我们，这种反应的关键信号转导器被上调，而修复蛋白被下调。然而，对这些改变如何导致辐射抗性的全面了解尚未到来。