The role of NFkB in the progression of breast and prostate cancer (HLS/DRFAPP7P/61999)

The increase in cancer incidence is evidenced by recent statistics suggesting that 1:2 people in the UK will develop the disease during their life. The most common forms of cancer in males and females are those of the prostate and mammary gland respectively, making research into these conditions of great importance. Of particular interest are new therapeutic targets potentially allowing specific focus on aggressive, metastatic cancers which are associated with a poor prognosis.

One potential target is Nuclear Factor kappa B (NFkB) which promotes an aggressive phenotype in both breast and prostate cancer. We have previously shown that inhibition of NFkB using DNA repair inhibitors such as PARP inhibitors can sensitise breast cancer cells to ionising radiation and chemotherapeutic agents. These findings highlighted the importance of NFkB status in tumours for the design of therapeutic strategies and the potential of repair inhibitors to overcome NFkB mediated therapeutic resistance (Hunter et al. 2012).

PARP inhibitors have recently been approved by the FDA for clinical use; further research is needed to elucidate other novel ways of using these drugs (and other repair inhibitors) to provide personalised cancer therapy. Our previous work studied the impact of these drugs on cell survival and death. The first aim of this project will be to screen other cell behaviours that go wrong in cancer progression. We will use well established kinetic (Xcelligence) and end-point assays to study how PARP inhibitors impact on cell migration, invasion and adhesion, which are deregulated in metastatic progression. By using well characterised sets of cells derived from normal and cancerous cells of breast or prostate origin in the presence or absence of repair inhibitors, we will further demonstrate their importance as a novel mechanism of selectively targeting cancer cells that have constitutive overexpression of NFkB. We will combine this with studies investigating whether PARP inhibitors change the action of tumour suppressive maspin. A recent study in Nature showed that a reason that men get prostate cancer is because of the loss of maspin expression via a pathway downstream of NFkB. The relationships between maspin and NFkB will be determined in cell lines +/- NFkB and +/- maspin.

Enquiries regarding this studentship should be made to: Dr Stephany Veuger, 0191 227 7627 [Email Address Removed]

For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/
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