Drug Repurposing for Mesothelioma Prevention in High-Risk Populations

Mesothelioma, a type of thoracic cancer, is a fatal malignancy most often associated with asbestos exposure, where the majority of those affected die within a year of diagnosis. The long latency period between first exposure and clinical diagnosis provides ample opportunity for therapeutic interventions that prevent or delay cancer development. However, there are currently no preventive options available for high-risk, exposed populations. The discovery of efficacious therapies for use in these individuals is urgently needed and would have the potential to substantially reduce mesothelioma mortality.

One of the main considerations in selecting active agents for therapeutic prevention is safety and tolerability because the ultimate intention is to give them to ‘healthy’ disease-free populations to try and prevent cancer, or prevent the recurrence/progression of cancer. Existing drugs in widespread use for other indications (e.g. aspirin and metformin) that possess a favourable safety profile present excellent candidates for translating to prevention. Drug repurposing, the use of approved established drugs for a new indication, is receiving considerable attention as an attractive alternative to traditional development pathways in oncology. It is increasingly apparent that diverse diseases share common molecular pathways and cellular targets, therefore, the vast majority of approved drugs are likely to have value in more than one therapeutic area; this is the underlying rationale of repurposing.

The overall aim of this project is to identify drugs with potential for repurposing in mesothelioma prevention. The successful applicant will focus on preclinical discovery and development using state-of-the-art platforms and clinically relevant models. They may also be involved in developing biomarkers for the early detection of mesothelioma and monitoring of disease progression and response to preventive interventions.

The successful applicant will be involved in high throughput screening of drugs in cell lines, followed by further assessment and mechanistic studies in patient-derived cell culture models (including stem cell spheroid and ex vivo explant cultures), and preclinical evaluation of efficacy.

The successful applicant will be based in the Chemoprevention Group under the primary supervision of Professor Karen Brown but will also benefit from significant input from clinical staff with expertise in medical oncology (Professors Anne Thomas and Dean Fennell), Professor Jacqui Shaw (expertise in genetic biomarkers), and colleagues in the MRC Toxicology Unit (Professor Marion MacFarlane).

We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups

We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.