Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Department of Radiation Oncology, OSUCCC and Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA.
Br J Cancer. 2023 Feb;128(3):407-412. doi: 10.1038/s41416-022-02041-9. Epub 2022 Nov 7.
Pivotal research led by Louis Harold Gray in the 1950s suggested that oxygen plays a vital role during radiotherapy. By proving that tumours have large necrotic cores due to hypoxia and that hypoxic cells require significantly larger doses of ionising radiation to achieve the same cell kill, Thomlinson and Gray inspired the subsequent decades of research into better defining the mechanistic role of molecular oxygen at the time of radiation. Ultimately, the work pioneered by Thomlinson and Gray led to numerous elegant studies which demonstrated that tumour hypoxia predicts for poor patient outcomes. Furthermore, this subsequently resulted in investigations into markers and measurement of hypoxia, as well as modification strategies. However, despite an abundance of pre-clinical data supporting hypoxia-targeted treatments, there is limited widespread application of hypoxia-targeted therapies routinely used in clinical practice. Significant contributing factors underpinning disappointing clinical trial results include the use of model systems which are more hypoxic than human tumours and a failure to stratify patients based on levels of hypoxia. However, translating the original findings of Thomlinson and Gray remains a research priority with the potential to significantly improve patient outcomes and specifically those receiving radiotherapy.
20 世纪 50 年代，路易斯·哈罗德·格雷（Louis Harold Gray）的重要研究表明，氧气在放射治疗过程中起着至关重要的作用。通过证明肿瘤由于缺氧而具有较大的坏死核心，并且缺氧细胞需要显著更大剂量的电离辐射才能达到相同的细胞杀伤效果，汤姆林森（Thomlinson）和格雷（Gray）激发了随后几十年对更好地定义辐射时分子氧的机制作用的研究。最终，汤姆林森（Thomlinson）和格雷（Gray）的开创性工作导致了许多精美的研究，这些研究表明肿瘤缺氧预示着患者预后不良。此外，这随后导致了对缺氧标志物和测量的研究，以及修饰策略的研究。然而，尽管有大量支持缺氧靶向治疗的临床前数据，但在临床实践中常规使用的缺氧靶向治疗的应用有限。导致临床试验结果令人失望的重要因素包括使用比人类肿瘤更缺氧的模型系统，以及未能根据缺氧水平对患者进行分层。然而，将汤姆林森（Thomlinson）和格雷（Gray）的原始发现转化仍然是一个研究重点，具有显著改善患者预后的潜力，特别是那些接受放射治疗的患者。
