The additional mechanistic role of hypoxia in the acquisition of aggressive prostate cancer phenotypes on the background of BRCA1/BRCA2 genetic deficiency is not known (Lalonde et al; Lancet Oncology, 2014; Chan et al; Mol.Can Res; 2014; Chua at al; Eur Urol., 2017).

We aim to develop and utilise isogenic models defective in BRCA1 and BRCA2 and determine the additional effect of hypoxia on the generation of genetic instability, HR repair and sensitivity to inhibitors of DNA repair machinery including those targeting ATM, ATR and DNA-PKcs using both in vitro and in vivo systems. We’re interested in the effects of hypoxia on genetic instability, and we aim to explore these using whole genome sequencing approaches and RNA seq. Understanding the mechanism by which hypoxia drives genetic instability in the absence and presence of underlying DNA repair defects may allow for better patient stratification using precision medicine for optimal prostate cancer treatment.