바로가기  >

Abstract
Radiotherapy (RT) is essential to the treatment of most solid tumors and acquired or innate resistance to this therapeutic modality is a major clinical problem. Here we show that miR-139-5p is a potent modulator of radiotherapy response in breast cancer (BC) via its regulation of genes involved in multiple DNA repair and reactive oxygen species defense pathways. Treatment of breast cancer cells with a miR-139-5p mimic strongly synergized with radiation both in vitro and in vivo, resulting in significantly increased oxidative stress, accumulation of unrepaired DNA damage and induction of apoptosis. Several miR-139-5p target genes were also strongly predictive of outcome, specifically in RT-treated patients across multiple independent breast cancer cohorts. These prognostically relevant miR-139-5p target genes were used as companion biomarkers to identify radioresistant BC xenografts highly amenable to sensitization by co-treatment with a miR-139-5p mimetic.

Author information

Pajic M1, Froio D2, Daly S2, Doculara L2, Millar E3, Graham PH4, Drury A2, Steinmann A2, de Bock CE5, Boulghourjian A2, Zaratzian A2, Carroll S6, Toohey J6, O'Toole SA7, Harris AL8, Buffa FM8, Gee HE9, Hollway GE2, Molloy TJ10.
1
Personalised Cancer Therapeutics, Cancer Division, The Kinghorn Cancer Centre, The Garvan Institute of Medical Research.
2
Cancer Research Division, The Kinghorn Cancer Centre / Garvan Institute of Medical Research.
3
The Kinghorn Cancer Centre.
4
St George Hospital.
5
VIB-KU Leuven Center for Cancer Biology, KU Leuven.
6
N/A, The Chris O'Brien Lifehouse.
7
Cancer Research Program, Garvan Institute of Medical Research.
8
Department of Oncology, University of Oxford.
9
Medicine, University of Sydney.
10
Blood, Stem Cell, and Cancer Research Group, St Vincent's Hospital Centre for Applied Medical Research t.molloy@amr.org.au.