Malignant mesothelioma (MM) is a rare, invariably fatal malignancy associated with asbestos exposure that occurs most frequently in the pleura. Treatment options are limited – the current gold standard chemotherapy regimen offers a median survival of 12.1 months versus 7 months for palliative therapy. There is thus a compelling need for more effective therapies.
TNF related apoptosis inducing ligand (TRAIL) is capable of inducing apoptosis selectively in cancer cells in vitro and in vivo. Whilst robust anti-cancer activity has been demonstrated in preclinical studies, results from clinical trials have proven disappointing. A number of reasons are possible including the absence of a validated biomarker for TRAIL sensitivity.
We have discovered a new biomarker for TRAIL sensitivity. This PhD project will delineate the mechanisms behind this with a view to building an application for a Phase1/2 study within the lifetime of the project.
1. To validate the biomarker / TRAIL effect in vitro through knock out and knock in studies in mutant and wild type (WT) MM cell lines.
2. To determine the mechanism by which biomarker alters TRAIL sensitivity in MM
3. To validate the biomarker / TRAIL effect in vivo using xenograft and genetically modified mouse models using recombinant TRAIL and available TRAIL agonists found safe in Phase1/2 studies
For informal enquiries please contact Professor Sam Janes: [email protected]
Physicians who are GMC-registered, meet UCL general admissions criteria, and qualify as UK/EU fee payers. These three year PhD studentships, funded by Cancer Research UK, includes a competitive clinical training salary, consumables funding, a travel allowance, and tuition fees (home/EU rate) paid in full.
To apply please e-mail the following pieces of information to [email protected]
and provide the project number(s)* in the subject line.
1. A CV highlighting your academic achievement, clinical training, and research interest/experience, as well as stating your nationality and usual country of residence
2. A short summary (<500 words) detailing how your research interests and academic background matches the project
3. Contact details for two referees
*One application per candidate please. Although you may list more than one project per application, your short summary will need to specify how your background/interests fit each project.
Application Deadline: Applications accepted until 5.00pm 12th February 2015
Initial receipt of your application will be acknowledged. Short-listing and interviews to be done in February/March 2016. Queries about the application procedure or recruitment process should be directed to: [email protected]