Image - Example of immunofluorescence image of day-four ex-vivo bladder tumour suspension showing the differential growth of cellular components.
For ex-vivo screening, we dissociate human tumours into their individual cellular components (epithelial, stromal, immune) and seed them on pre-loaded, cancer-specific 384-well drug plates. After four days in incubation, plates are fixed and immunofluorescence analysis is used to determine tumour responses to different treatments.
Samantha’s preliminary work on this project led to the successful acquisition of The Urology Foundation Research Scholarship Award 2020, worth £60,000 – which has facilitated significant progression in methodological processes during her out-of-programme research. In the last four months, the project has recruited over 30 patients to the study. Initially, the focus of the project was optimising tissue logistics, dissociation techniques and immunofluorescence protocols, in parallel to identical validation plates for which they have completed enzymatic analysis on. Currently, they have generated end-point patient-specific drug-sensitivity results for 17 patients. From these results, they are able to identify dose dependent responses of the dissociated tumour tissue (for each individual patient), to standard of care, novel and repurposed oncological therapies. More recently, this has expanded to include immunotherapies.
The ex-vivo screening model is an exciting and novel tool that has huge potential in oncological disease – not only in improving patient treatment selection, but also in expediting novel drug discovery. Hopefully, in the future, the methodology used in this pre- clinical model can be translated for use in other solid cancer types; this is being discussed as part of the EVIDENT (Ex-vivo multi-drug screening of solid tumours to determine personalised therapy efficacy and resistance) consortium.
Bio
Miss Samantha Conroy is an ST3-equivalent urology trainee undertaking out-of-programme research to complete a staff-candidate PhD at the University of Sheffield. Samantha completed her undergraduate medical training in Nottingham, which provided her with the opportunity to complete a Biomedical Sciences degree in parallel to her studies. She moved to Sheffield in 2014 to begin her academic foundation training; during this time, she spent four months completing medical education training and acquired a post-graduate certificate in medical education. More recently, Samantha was appointed as an NIHR Academic Clinical Fellow in Urology. She worked in the Department of Oncology and Metabolism on a six-month placement alongside the Helleday Group, where she was given the opportunity to learn a range of lab skills and techniques. With the help of Dr Wells and other members of the laboratory team, and the guidance of Prof Catto and Prof Helleday, Samantha pioneered the ex-vivo high-throughput drug screening (ex-vivo screening) in human bladder cancers.