About Professor Rob Bristow

Almost 50,000 men living in the UK will be diagnosed with prostate cancer (PCa) every year and its incidence is increasing every year. High-risk prostate cancers fail multimodal therapy using radiotherapy and or surgery at least 20% of the time and these failures are responsible for the majority of prostate cancer deaths at 10 years. There is a real need to develop new biomarkers, including ones speaking to aggressive genomic evolution, that give an insight into heterogeneity of outcomes in prostate cancer patients in the setting of  both sporadic and hereditary cancers.

In recent years, there has been a growing appreciation of the role of DNA damage response and repair (DDR) genes,  such as BRCA2, MSH2 and ATM,  in the biology PCa aggression. In depth analyses of the prostate cancer genome have shown that somatic mutations in DNA repair genes are relatively frequent and are more common in incurable, castrate-resistant disease (mCRPC) than in primary cancers. Concordantly, it has been shown that men carrying germline mutations in such genes are at a higher risk of developing prostate cancers that progress to become metastatic.

The presence of hypoxia in PCa is also correlated with a poor prognosis and several factors may contribute to this observation, including resistance to radiotherapy leading to failure of local control, impaired DNA repair, and adaptive responses that promote metastasis. As hypoxia is tightly correlated with levels of genome instability and polyclonality across a range of cancer types, we also wish to understand the interaction between the tumour microenvironment (TME) and the mutator phenotype. DDR and hypoxia signalling pathways are also potential co-factors in determining the aggression of penile cancers which are driven by HPV insertion and genetic programming,

Our lab therefore studies genotype-phenotype interactions using primary or ex vivo human cancer models for multi-omic and functional genomic studies.