Research Interests

I am currently a SCREDS (Scottish Clinical Research Excellence Development Scheme) funded Clinical Lecturer at The CRUK Beatson Institute/ University of Glasgow and a Specialist Registrar in Medical Oncology at the Beatson West of Scotland Cancer Centre.

During my PhD, which was undertaken in the Beatson Institute under the supervision of Professor Karen Vousden and Professor Jeff Evans, I studied the mechanism of action of drugs designed to restore the tumour suppressive functions of p53 to treat cancer. Currently, as part of Professor Karen Vousden’s group, I now focus my research on studying various methods of manipulating the p53 pathway for cancer treatment. 

The p53 pathway is a tumour suppressor pathway that becomes dysfunctional in most cancers.  This can happen by a variety of different mechanisms including up regulation of the negative regulators of p53 (Mdm2 and MdmX) and mutation of p53 itself.  Importantly the most appropriate method of wild-type p53 restoration for cancer treatment depends on the specific mechanism of dysfunction of the p53 pathway present in a tumour.

In some types of cancer p53 mutations are relatively rare (prostate cancer); therefore for these cancers, inhibition of p53’s negative regulators may be useful to reactivate the remaining wild-type p53 (Figure 1).  In cancers where a p53 mutation is present (ovarian cancer) a different approach is needed.

Patricia Roxburgh - mutation rate graph

Figure 1: p53 mutation rate by primary site. Generated from the International Agency for Research on Cancer (IARC) p53 database (R17, Nov 2013).

The MAdCaP trial is a clinical study investigating inhibition of Mdm2 in the treatment of castration resistant prostate cancer. The study is led by Chief Investigator Dr Rob Jones on behalf of the UK National Cancer Research Institute Prostate Cancer Clinical Studies Group.  My role is as translation lead in this collaboration between the University of Glasgow, Glasgow Cancer Research UK Clinical Trials Unit, NHS Greater Glasgow and Clyde and Roche.

Patricia Roxburgh - 3 logo image

In MAdCAP, patients with metastatic castration resistant prostate cancer who have not previously received docetaxel will receive abiraterone acetate with or without the Mdm2 inhibitor RO5503781.

Patients will be asked to consent for access to archival tumour samples and have the option of having biopsies on entering the trial, during treatment and also at progression to allow study of the p53 pathway in prostate cancer. Blood and urine sampling will also take place throughout the study to allow pharmacokinetic and pharmcodynamic studies.

In contrast with prostate cancer, high-grade serous ovarian cancers (HGSC) have very high rates of p53 mutations (Figure 1). For these cancers alternative approaches to inhibit the cancer promoting functions of mutant p53 need to be developed. In collaboration with Professor Iain McNeish and the Scottish Gynaecological Clinical Trials Group, I am studying the relationship between p53 mutation, inflammatory cell infiltrates and NF-κB signaling since inflammatory cell infiltrates have been associated with survival in HGSC (Figure 2) and more recently promotion of pro-tumour inflammation has been reported as a p53 gain of function mechanism in cell based models.  Importantly, identifying inflammation as a driving mechanism in HGSC will lead to new treatment approaches.

 ‌Patricia Roxburgh - HGS Ovarian Cancer

 Figure 2: Cell types associated with poor survival (red) and good survival (green).