Molecular targeting of hypoxia in radiotherapy

Sergio Rey; Luana Schito; Marianne Koritzinsky; Bradly G Wouters

doi:10.1016/j.addr.2016.10.002

Molecular targeting of hypoxia in radiotherapy

Adv Drug Deliv Rev. 2017 Jan 15:109:45-62. doi: 10.1016/j.addr.2016.10.002. Epub 2016 Oct 19.

Authors

Sergio Rey¹, Luana Schito¹, Marianne Koritzinsky², Bradly G Wouters³

Affiliations

¹ Princess Margaret Cancer Centre and The Campbell Family Institute for Cancer Research, University Health Network, Toronto, Ontario, Canada.
² Princess Margaret Cancer Centre and The Campbell Family Institute for Cancer Research, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
³ Princess Margaret Cancer Centre and The Campbell Family Institute for Cancer Research, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Electronic address: bwouters@uhnresearch.ca.

PMID: 27771366
DOI: 10.1016/j.addr.2016.10.002

Abstract

Hypoxia (low O₂) is an essential microenvironmental driver of phenotypic diversity in human solid cancers. Hypoxic cancer cells hijack evolutionarily conserved, O₂- sensitive pathways eliciting molecular adaptations that impact responses to radiotherapy, tumor recurrence and patient survival. In this review, we summarize the radiobiological, genetic, epigenetic and metabolic mechanisms orchestrating oncogenic responses to hypoxia. In addition, we outline emerging hypoxia- targeting strategies that hold promise for individualized cancer therapy in the context of radiotherapy and drug delivery.

Keywords: Cancer Metabolism; Drug Delivery; HIF; Hypoxia; Hypoxia Tolerance; Ionizing Radiation; ROS; Radiosensitizers; Targeted Cancer Therapy; Tumor Microenvironment; UPR.

Publication types

Review

MeSH terms

Cell Hypoxia / genetics
Cell Hypoxia / radiation effects*
Epigenesis, Genetic
Humans
Molecular Targeted Therapy*
Neoplasms / genetics
Neoplasms / metabolism*
Neoplasms / pathology
Neoplasms / radiotherapy*
Oxygen / metabolism*

Substances

Oxygen