GW4 BioMed MRC DTP PhD Studentship: Anti-cancer immunity, liquid biopsies and lifestyle factors as predictors of breast cancer treatment outcomes

This project is one of a number that are in competition for funding from the ‘GW4 BioMed MRC Doctoral Training Partnership’ which is offering up to 19 studentships for 2018.

The DTP brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities. The training programme has three strands: research skills; professional and career development skills; and opportunities to broaden horizons, which might include placements, research visits, public engagement internships and a mini-MD programme of bespoke clinical exposure.

Supervisory team for this project:
Dr James Turner (Bath), Prof Mark Beresford (Royal United Hospital, Bath), Dr Robert Jones (Cardiff) and Dr Rachel Butler (University Hospital of Wales)

BACKGROUND:
The most common cancer in the UK is breast cancer with approximately 55,000 new female cases each year. Many women are treated with neodjuvant chemotherapy prior to surgery and the success of this regimen can be assessed by measuring changes to tumour size with treatment using imaging. Tumour shrinkage exhibited by some women is evidence of effective chemotherapy, which is in part, mediated by anti-cancer immunity. However, an increase or no change in tumour size in other women is evidence of ineffective chemotherapy, implying high tumour activity and perhaps impaired immune function. Recent studies in several cancers have shown that strong anti-cancer immunity predicts positive treatment outcomes. Other studies have shown that high levels of cell-free tumour DNA, assessed in plasma as a measure of tumour activity and referred to as a liquid biopsy, predicts negative treatment outcomes. Thus, measuring cancer-specific immunity and collecting liquid biopsies may allow the balance between anti-cancer and pro-cancer processes to be assessed, which might have utility in monitoring treatment. These measurements however have never been assessed in parallel and validated against other established methods for assessing treatment progress and outcomes.

PROJECT OVERVIEW:
This work, will for the first time, assess cancer-specific immunity and cell-free tumour DNA in tandem, validating their predictive utility in breast cancer neoadjuvant chemotherapy, which can be monitored sensitively and non-invasively with imaging. In addition, this project, unlike most research seeking predictive biomarkers, will consider lifestyle variables that are known to interact with immune function and have been linked to clinical outcomes. For example, physically active people exhibit better immune competence (e.g. stronger antibody responses to vaccination) than inactive people, and high cardiorespiratory fitness is linked to better clinical outcomes in patients. Mechanistic studies in humans and mice suggest these observations are linked, showing that exercise bolsters anti-cancer immunity. Thus, if biomarkers for predicting inter-patient variation in treatment effectiveness are to be established, it is essential to control for lifestyle factors that show inter-individual variation in the population.

TRAINING:
This PhD studentship will provide cutting edge training at four levels of scientific investigation. First, analysis of cancer-specific processes at the molecular level, such as next generation sequencing of tumour DNA (Cardiff, Jones and Butler). Second, analysis of immune function at the cellular level, such as flow cytometry (Bath, Turner). Third, assessment of lifestyle variables at a broader physiological level, including cardiorespiratory fitness, habitual physical activity and body composition (Bath; Turner). Fourth, analysis and interpretation of anonymised clinical information such as imaging data (Royal United Hospital Bath; Beresford).


IMPORTANT: In order to apply for this project, you should apply using the DTP’s online application form. More information on the application process may be found here: http://www.gw4biomed.ac.uk/projects-2/for-students/

APPLICATIONS OPEN ON 25 SEPTEMBER AND CLOSE AT 17:00 ON 24 NOVEMBER 2017.

You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application to study at Bath.