Exploring hypoxic biology to improve radiotherapy outcomes

Li, Chun; Wiseman, Lucy; Okoh, Ene; Lind, Michael; Roy, Rajarshi; Beavis, Andrew; Monteiro dos Santos Pires, Isabel

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 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 pro-drugs (HAPs), 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.

Citation

Li, C., Wiseman, L., Okoh, E., Lind, M., Roy, R., Beavis, A., & Monteiro dos Santos Pires, I. (2022). Exploring hypoxic biology to improve radiotherapy outcomes. Expert Reviews in Molecular Medicine, 24, Article E21. https://doi.org/10.1017/erm.2022.14

• Journal Article Type: Article
• Acceptance Date: Apr 12, 2022
• Online Publication Date: Apr 27, 2022
• Publication Date: 2022
• Deposit Date: Apr 27, 2022
• Publicly Available Date: Oct 28, 2022
• Journal: Expert Reviews in Molecular Medicine
• Print ISSN: 1462-3994
• Publisher: Cambridge University Press
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Article Number: E21
• DOI: https://doi.org/10.1017/erm.2022.14
• Public URL: https://hull-repository.worktribe.com/output/3984679