Sarcoma Molecular Pathology Team, The Institute of Cancer Research, London, UK.
Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Surrey, UK.
Br J Cancer. 2021 Feb;124(3):539-551. doi: 10.1038/s41416-020-01107-w. Epub 2020 Oct 27.
In tumours, hypoxia-a condition in which the demand for oxygen is higher than its availability-is well known to be associated with reduced sensitivity to radiotherapy and chemotherapy, and with immunosuppression. The consequences of hypoxia on tumour biology and patient outcomes have therefore led to the investigation of strategies that can alleviate hypoxia in cancer cells, with the aim of sensitising cells to treatments. An alternative therapeutic approach involves the design of prodrugs that are activated by hypoxic cells. Increasing evidence indicates that hypoxia is not just clinically significant in adult cancers but also in paediatric cancers. We evaluate relevant methods to assess the levels and extent of hypoxia in childhood cancers, including novel imaging strategies such as oxygen-enhanced magnetic resonance imaging (MRI). Preclinical and clinical evidence largely supports the use of hypoxia-targeting drugs in children, and we describe the critical need to identify robust predictive biomarkers for the use of such drugs in future paediatric clinical trials. Ultimately, a more personalised approach to treatment that includes targeting hypoxic tumour cells might improve outcomes in subgroups of paediatric cancer patients.
在肿瘤中，缺氧——一种氧气需求高于其供应的情况——众所周知与放疗和化疗敏感性降低以及免疫抑制有关。缺氧对肿瘤生物学和患者预后的影响导致人们研究可以减轻癌细胞缺氧的策略，目的是使细胞对治疗更敏感。另一种治疗方法涉及设计由缺氧细胞激活的前药。越来越多的证据表明，缺氧不仅在成人癌症中具有临床意义，而且在儿科癌症中也是如此。我们评估了评估儿童癌症中缺氧水平和程度的相关方法，包括氧气增强磁共振成像 (MRI) 等新的成像策略。临床前和临床证据在很大程度上支持在儿童中使用缺氧靶向药物，我们描述了确定此类药物在未来儿科临床试验中使用的稳健预测生物标志物的迫切需要。最终，包括针对缺氧肿瘤细胞的更个性化治疗方法可能会改善某些儿科癌症患者亚组的治疗效果。
