Identifying mechanisms of drug resistance in endometrial cancer

This studentship is funded by the Leicester Precision Medicine Institute (LPMI) and is placed within the supportive and nurturing environment provided by the Leicester Institute of Precision Medicine, the Leicester Biomedical Research Centre and the Leicester Centre for Cancer Research. You will receive financial backing and the support of an inclusive and collaborative research culture - enabling you to realise your potential.

Endometrial cancer (EC) is the most common gynaecological malignancy in developed countries and is known to have ethnic differences in disease profile and survival. The prognosis of advanced/metastatic EC is poor due to low response rates to the current drug options. One reason for this is that current pre-clinical models fail to replicate intra-tumour heterogeneity and tumour-stromal interactions, therefore are not representative of the genetic changes demonstrated across sub-populations of tumour cells.

We have developed a novel patient derived explant (PDE) platform in EC which maintains viability across both tumour/stroma for up to 48-hours in culture across all EC subtypes and have reported evidence of differential drug response following culture with cytotoxic agents to provide proof of concept for use of this platform for drug response studies. This PDE model truly captures tumour heterogeneity and preserves a personalised tumour microenvironment reflective of in-vivo conditions, unlike other preclinical model systems, therefore represents a powerful platform for pre-clinical modelling, drug response studies and personalized medicine in EC.

Following drug treatment, PDEs are processed for spatial biomarker analysis. Multi-immunofluorescence (mIF) analysis of biomarker expression is performed using cutting-edge digital methods, allowing assessment of the effects of a therapeutic agent in tumour/non-tumour regions, enabling tracking of multiple cell types in the tumour stroma in response to drug treatment. This is particularly important for analysing PDE responses to immune checkpoint inhibitors (ICIs), which have shown exciting promise in a proportion of EC cases. Indeed, our preliminary data indicate patient-specific responses of PDEs to immunotherapies, indicating the power of this this platform for evaluating ICI efficacy and in identifying novel biomarkers of response that could be used to stratify patients.

The aim of this project is to build on work already undertaken in EC and other tumour types by using standard of care and novel therapeutic agents to demonstrate the utility of the PDE platform in pre-clinical drug response studies, in order to attract industry investment for investigating other novel agents.

Entry requirements
UK Bachelor Degree with at least 2:1 in a relevant subject or overseas equivalent.

University of Leicester English language requirements apply (where applicable)