Hypoxia and its therapeutic possibilities in paediatric cancers.

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.

• Authors: Carolina Bernauer, Y K Stella Man, Julia C Chisholm, Elise Y Lepicard, Simon P Robinson, Janet M Shipley
• Journal: British journal of cancer (Br J Cancer) Vol. 124 Issue 3 Pg. 539-551 (02 2021) ISSN: 1532-1827 [Electronic] England
• PMID: 33106581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Biomarkers
• Glucose Transporter Type 1
• Hypoxia-Inducible Factor 1, alpha Subunit
• Nitroimidazoles
• Prodrugs
• SLC2A1 protein, human
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Carbonic Anhydrase IX

Topics

• Antineoplastic Agents (metabolism, therapeutic use)
• Biomarkers (metabolism)
• Carbonic Anhydrase IX (antagonists & inhibitors, metabolism)
• Cell Hypoxia (genetics, physiology)
• Child
• Combined Modality Therapy (methods)
• Glucose Transporter Type 1 (antagonists & inhibitors, metabolism)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, metabolism)
• Magnetic Resonance Imaging (methods)
• Neoplasms (diagnostic imaging, metabolism, therapy)
• Nitroimidazoles (metabolism)
• Oxygen Consumption
• Prodrugs (metabolism, therapeutic use)
• Tumor Hypoxia (genetics, physiology)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, metabolism)