Hypoxia and its therapeutic possibilities in paediatric cancers |
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| Authors: | Carolina Bernauer Y. K. Stella Man Julia C. Chisholm Elise Y. Lepicard Simon P. Robinson Janet M. Shipley |
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| Affiliation: | 1.Sarcoma Molecular Pathology Team, The Institute of Cancer Research, London, UK ;2.Children and Young People’s Unit, The Royal Marsden NHS Foundation Trust, Surrey, UK ;3.Sarcoma Clinical Trials in Children and Young People Team, The Institute of Cancer Research, London, UK ;4.Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK |
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| Abstract: | 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.Subject terms: Tumour biomarkers, Paediatric cancer, Cancer microenvironment, Cancer therapy |
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