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(Leeds-Manchester Clinical) Rationally Developing the Next Generation of Personalised Target Drug-Chemotherapy Combination Trials in Anal Cancer

Faculty of Medicine and Health

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Dr A Samson No more applications being accepted Funded PhD Project (Students Worldwide)

About the Project

Anal cancer incidence is rapidly rising. Chemo-radiotherapy is the standard of care for the majority of localised anal cancers and is given with curative intent. The CRUK PLATO trial is a flagship clinical platform led by Leeds Clinical Trials Unit to determine whether radiotherapy dose escalation will reduce loco-regional failure in patients with high risk disease. For these patients alternative future treatment strategies are required. Funded by CRUK this project is a unique opportunity to undertake world-leading collaborative oncology clinical trials research at the Leeds Institute of Clinical Trials Research, University of Leeds, and the Manchester Experimental Cancer Medicine Centre, University of Manchester

1. To identify chemo-radiotherapy anal cancer immune resistance mechanisms and to correlate these with clinical outcomes in patients with high-risk anal cancer enrolled in the PLATO trial.
2. To inform improvements in treatment outcomes by targeting recurrent radiotherapy immune resistance mechanisms in pre-clinical models of anal cancer.
3. To rationally inform and assist novel early-phase clinical trial design to integrate immunotherapy into future curative anal cancer trials.

This project will identify the principal radiotherapy immune resistance mechanisms in anal cancer, during and after chemo-radiotherapy, through a translational study of serial peripheral blood samples from patients with locally advanced anal cancer within the PLATO trial. Blood samples will be analysed by flow cytometry immunophenotyping and multiplex cytokine quantification. The identified therapeutic targets will be investigated in in vitro and in vivo pre-clinical models of anal cancer, in combination with radiotherapy, to rationally bring forward immunotherapy drugs for combination studies. The laboratory data will inform a rationalised combination clinical trial in patients with high-risk anal cancer, using key trial design characteristics, biomarker enrichment and platform approaches to evaluate multiple therapies.

The student will receive unique training in translational laboratory techniques, acquire expertise in the delivery of early-phase immunotherapy trials at the Manchester Experimental Cancer Medicine Centre and learn novel methodological and statistical skills at the Leeds Clinical Trials and Research Unit, University of Leeds.

You should hold a first degree equivalent to at least a UK upper second class honours degree in Medicine. All applicants should be post-registration clinicians and ideally hold a core or specialist training post. It is generally expected that Clinical PhD Fellows would return to a training programme in the UK upon completion of their research degree.

Candidate whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study, the Faculty minimum requirements are:

• British Council IELTS - score of 6.5 overall, with no element less than 6.0
• TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

How to apply
To apply for this project applicants should complete a Faculty Application form using the link below and send this alongside a 1000 word personal statement, a full academic CV, degree certificates and transcripts (or marks so far if still studying) to the Faculty Graduate School at [Email Address Removed]

Personal Statement Guidance: please comment on your suitability for the post, giving an overview of your relevant experience and training. This should summarise:
•    Your motivation for postgraduate research study;
•    Why you want to do a postgraduate research degree in Leeds;
•    Any research experience that you have. If you have previously completed a research project please give a short description of the work you undertook, including the research problem, your key findings and any techniques acquired and skills learned.

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly to [Email Address Removed] by no later than Sunday 29 November

Any queries regarding the application process should be directed to [Email Address Removed]

Informal enquiries about this project can be sent directly to Dr Adel Samson [Email Address Removed]

Funding Notes

This fellowship is funded by Cancer Research UK and will provide running expenses, an appropriate salary in line with the applicant’s current clinical salary, and academic fees at the UK fee rate. If you are an EU/International applicant you must be able to demonstrate that you can fund the deficit in fees between the UK an International fee rate at the time of application.
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