Tumor hypoxia as a driving force in genetic instability

Kaisa R Luoto; Ramya Kumareswaran; Robert G Bristow

doi:10.1186/2041-9414-4-5

Tumor hypoxia as a driving force in genetic instability

Genome Integr. 2013 Oct 24;4(1):5. doi: 10.1186/2041-9414-4-5.

Authors

Kaisa R Luoto^#¹, Ramya Kumareswaran^#^{1

2}, Robert G Bristow^{1

2}

Affiliations

¹ Ontario Cancer Institute, Radiation Medicine Program, Princess Margaret Cancer Centre (University Health Network), Toronto, ON, Canada.
² Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre (University Health Network), 610 University Avenue, Toronto, ON M5G2M9, Canada.

^# Contributed equally.

Abstract

Sub-regions of hypoxia exist within all tumors and the presence of intratumoral hypoxia has an adverse impact on patient prognosis. Tumor hypoxia can increase metastatic capacity and lead to resistance to chemotherapy and radiotherapy. Hypoxia also leads to altered transcription and translation of a number of DNA damage response and repair genes. This can lead to inhibition of recombination-mediated repair of DNA double-strand breaks. Hypoxia can also increase the rate of mutation. Therefore, tumor cell adaptation to the hypoxic microenvironment can drive genetic instability and malignant progression. In this review, we focus on hypoxia-mediated genetic instability in the context of aberrant DNA damage signaling and DNA repair. Additionally, we discuss potential therapeutic approaches to specifically target repair-deficient hypoxic tumor cells.