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Defining the genetic determinants of mismatch repair deficient tumours that predicts response to immune checkpoint blockade


Project Description

Our Institute has an international reputation for cancer research, with world renowned experts in the field.
As part of our comprehensive training programme, fully funded by Cancer Research UK, we have funding for 3 PhD studentships to commence in September 2020.
Our training programme aims to develop a cohort of scientists equipped both intellectually and technically to conduct the highest quality research on cancer.
Our research degrees are supplemented by a comprehensive support programme, providing training in a wide range of biomedical laboratory methods and other vital transferable skills.

Inhibition of the immune checkpoint molecules, PD-1, CTLA-4 and PDL-1 have recently shown great clinical promise in many cancers. However, definitive biomarkers for response to immune checkpoint inhibitors are lacking. A recent Phase II clinical trial in patients with deficiency in the DNA mismatch repair (MMR) pathway indicated that MMR status predicted clinical benefit with the PD-1 inhibitor, pembrolizumab. These findings have led to the first tissue-agnostic approval for anti PD-1 therapy for unresectable or metastatic solid tumours with MMR deficiency. However, it is becoming increasingly clear that many MMR deficient tumours fail to respond to anti-PD-1 therapy with approximately 50% refractory to treatment. Furthermore, in the proportion of those MMR-deficient patients that do respond, there is a wide diversity of clinical benefit. In this PhD proposal, we will use both CRISPR-Cas9 generated MMR deficient cancer cell lines and in vivo models to elucidate the precise genetic determinants upon MMR loss that may predict response to immune checkpoint blockade.

Academic Entry Requirements

This studentship is open to graduates with either:
- a 2:1 or 1st degree in a related subject; or,
- a 2:2 in a related subject with a subsequent MSc awarded with Merit or Distinction
If your degree has not yet been awarded but you are expected to meet the above entry requirements, you are welcome to apply.

English Language Requirements

Applicants for whom English is not a first language will also require a minimum IELTS score of 6.5 (with 6.0 in the written component), or equivalent, unless your undergraduate degree was studied in, and awarded by, an English speaking country.

Funding Notes

This studentship includes the following funding for 3 years:

- A tax-free annual stipend of £21,000
- Tuition fees at the Home/EU rate
- Project consumables

The funding for this studentship only covers tuition fees at the home/EU rate. Overseas applicants are welcome to apply, but will be required to fund the difference in tuition fees

Part-time students will receive pro-rata funding for 6 years.

How good is research at Queen Mary University of London in Clinical Medicine?

FTE Category A staff submitted: 144.11

Research output data provided by the Research Excellence Framework (REF)

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