Tumor Hypoxia Drives Genomic Instability

Ming Tang; Emma Bolderson; Kenneth J O'Byrne; Derek J Richard

doi:10.3389/fcell.2021.626229

Tumor Hypoxia Drives Genomic Instability

Front Cell Dev Biol. 2021 Mar 16:9:626229. doi: 10.3389/fcell.2021.626229. eCollection 2021.

Authors

Ming Tang^{1

2}, Emma Bolderson^{1

2}, Kenneth J O'Byrne^{1

2

3}, Derek J Richard^{1

2}

Affiliations

¹ Centre for Genomics and Personalised Health, Queensland University of Technology (QUT), Brisbane, QLD, Australia.
² Cancer and Ageing Research Program, Translational Research Institute, Brisbane, QLD, Australia.
³ Princess Alexandra Hospital, Brisbane, QLD, Australia.

Abstract

Cancer is a leading cause of death worldwide. As a common characteristic of cancer, hypoxia is associated with poor prognosis due to enhanced tumor malignancy and therapeutic resistance. The enhanced tumor aggressiveness stems at least partially from hypoxia-induced genomic instability. Therefore, a clear understanding of how tumor hypoxia induces genomic instability is crucial for the improvement of cancer therapeutics. This review summarizes recent developments highlighting the association of tumor hypoxia with genomic instability and the mechanisms by which tumor hypoxia drives genomic instability, followed by how hypoxic tumors can be specifically targeted to maximize efficacy.

Keywords: DNA damage repair; DNA damage response; HIF-1α; cancer therapeutic resistance; conceptual lethality; genomic instability; tumor hypoxia.

Publication types

Review