Ewing sarcoma is the second most common bone tumour in children and young adults. Relapse (where the disease returns after treatment) is relatively common. Up to 80% of patients who present with metastatic Ewing sarcoma: where it has spread to other parts of the body, experience relapse. There are very few options available to treat recurrent (relapsed) Ewing sarcoma and as a result the outlook for pateints experiencing relapse is often dismal.
Based on their success in other sarcomas, tyrosine kinase inhibitors (TKIs) have been trialled, with mixed success, in patients with relapsed Ewing sarcoma. One of the main reasons TKIs have had mixed success is because we do not know the mechanisms underpinning their response. Therefore, we don’t know the right way to use TKIs e.g alongside other anti-cancer drugs or the right patients to give TKIs to i.e. which Ewings patients are most likely to have a good response to TKIs.
The purpose of this PhD is to determine the mechanisms underpinning response to TKIs in Ewing sarcoma patients, which will allow us to identify the right patients for TKIs and the best way to use TKIs in order to improve outcomes for Ewing sarcoma patients.
This project will provide a broad range of skills spanning material science to in vivo biology: employing state-of-the-art, bespoke bone-like mimetics in vitro and generating complex human-mimetic bone cancer models in vivo. The project will evaluate mechanisms of response to TKIs, focussing on immune-based effects, by employing a range of techniques in vitro and in vivo including FACS/CyTOF, ELISA, qRT-PCR and histology. In vivo studies will also benefit from access to the latest, cutting-edge technologies in molecular imaging and immune cell profiling (CYTOF). Findings from the in vivo tumour models will be cross validated in samples from patients, by analysing material from clinical trials of TKIs in Ewing sarcoma patients.
If successful, this project will provide new insight into the mechanism of response to TKIs in Ewings, particularly with respect to the immunological effects of these agents. This information can be used to drive more intuitive use of TKIs in the clinic and therefore improve outcomes for patients with recurrent Ewings, who so desperately need new, viable treatment options.
https://www.research.manchester.ac.uk/portal/en/researchers/martin-mccabe(03800398-2d17-49fb-9159-29f95cb7e95d)/projects.html?period=running
https://www.research.manchester.ac.uk/portal/K.G.Finegan.html
https://www.research.manchester.ac.uk/portal/kaye.williams.html
https://www.research.manchester.ac.uk/portal/sarah.cartmell.html
Entry Requirements
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.
How to Apply
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships
Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
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