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Exploring hypoxic biology to improve radiotherapy outcomes

Part of: Advancements in the radiobiology of low and high-LET radiation

Published online by Cambridge University Press:  27 April 2022

Chun Li ,
Lucy Wiseman ,
Ene Okoh ,
Michael Lind ,
Rajarshi Roy Open the ORCID record for Rajarshi Roy [Opens in a new window] ,
Andrew W. Beavis Open the ORCID record for Andrew W. Beavis [Opens in a new window]  and
Isabel M. Pires Open the ORCID record for Isabel M. Pires [Opens in a new window]
Chun Li
Affiliation:
Hypoxia and Tumour Microenvironment Lab, Department of Biomedical Sciences, Faculty of Health Sciences, University of Hull, Hull, UK
Lucy Wiseman
Affiliation:
Hypoxia and Tumour Microenvironment Lab, Department of Biomedical Sciences, Faculty of Health Sciences, University of Hull, Hull, UK
Ene Okoh
Affiliation:
Hypoxia and Tumour Microenvironment Lab, Department of Biomedical Sciences, Faculty of Health Sciences, University of Hull, Hull, UK
Michael Lind
Affiliation:
Queen's Centre for Oncology and Haematology, Castle Hill Hospital, Castle Rd, Cottingham HU16 5JQ, UK Faculty of Health Sciences, University of Hull, Cottingham Road, Hull, HU16 7RX, UK
Rajarshi Roy
Affiliation:
Queen's Centre for Oncology and Haematology, Castle Hill Hospital, Castle Rd, Cottingham HU16 5JQ, UK
Andrew W. Beavis
Affiliation:
Faculty of Health Sciences, University of Hull, Cottingham Road, Hull, HU16 7RX, UK Department of Medical Physics, Queen's Centre for Oncology, Hull University Teaching Hospitals NHS Trust, Cottingham, HU16 5JQ, UK Faculty of Health and Well Being, Sheffield-Hallam University, Collegiate Crescent, Sheffield, S10 2BP, UK
Isabel M. Pires*
Affiliation:
Hypoxia and Tumour Microenvironment Lab, Department of Biomedical Sciences, Faculty of Health Sciences, University of Hull, Hull, UK
*
Author for correspondence: Isabel M. Pires, E-mail: i.pires@hull.ac.uk
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Abstract

Ionising radiotherapy is a well-established, effective cancer treatment modality, whose efficacy has improved with the application of newer technological modalities. However, patient outcomes are governed and potentially limited by aspects of tumour biology that are associated with radioresistance. Patients also still endure treatment-associated toxicities owed to the action of ionising radiation in normoxic tissue adjacent to the tumour mass. Tumour hypoxia is recognised as a key component of the tumour microenvironment and is well established as leading to therapy resistance and poor prognosis. In this review, we outline the current understanding of hypoxia-mediated radiotherapy resistance, before exploring targeting tumour hypoxia for radiotherapy sensitisation to improve treatment outcomes and increase the therapeutic window. This includes increasing oxygen availability in solid tumours, the use of hypoxia-activated prodrugs, targeting of hypoxia-regulated or associated signalling pathways, as well as the use of high-LET radiotherapy modalities. Ultimately, targeting hypoxic radiobiology combined with precise radiotherapy delivery modalities and modelling should be associated with improvement to patient outcomes.

Keywords

DNA damage responseHAPsHIFhypoxiaradioresistanceradiotherapytargeted therapy
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 24 , 2022 , e21
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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