Hypoxia and its therapeutic possibilities in paediatric cancers.
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Authors
Bernauer, C
Man, YKS
Chisholm, JC
Lepicard, EY
Robinson, SP
Shipley, JM
Man, YKS
Chisholm, JC
Lepicard, EY
Robinson, SP
Shipley, JM
Document Type
Journal Article
Date
2021-02-02
Date Accepted
2020-09-11
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.
Citation
British journal of cancer, 2020
Source Title
Publisher
SPRINGERNATURE
ISSN
0007-0920
eISSN
1532-1827
Research Team
Sarcoma Clinical Trials in children and young people
Sarcoma Molecular Pathology
Pre-Clinical MRI
Sarcoma Clinical Trials in children and young people
Sarcoma Molecular Pathology
Pre-Clinical MRI
Sarcoma Molecular Pathology
Pre-Clinical MRI
Sarcoma Clinical Trials in children and young people
Sarcoma Molecular Pathology
Pre-Clinical MRI