Ex-vivo prostate culture utilising ‘PEOPLE’ – PatiEnt prOstate samPLes for rEsearch


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Susan Heavey1,Hayley Pye1,Lina Carmona Echeverria1,Greg Shaw2,Alex Freeman2,Marzena Ratynska2,Charles Jameson2,Helena Costa1,Sophia Jenkinson1,Georgina Lewis1,John Kelly2,Andrew Feber1,Hayley Whitaker1
1UCL,2UCLH

Abstract

Background

One of the major obstacles to overcome in prostate cancer research is the acquisition of high quality fresh human tumour samples for experimental use. Previously published work from our group has described a method for slicing and sampling human prostate tissue removed by radical prostatectomy, which preserves all margins for routine histopathological analysis, while also providing large volumes of fresh tissue for research. Our new project ‘PEOPLE – PatiEnt prOstate samPLes for rEsearch’ utilises this method with modifications to generate high quality fresh tissue for a number of downstream applications.

Method

Prostate cancer patients who have been recruited to the 100,000 genomes study are also consented for PEOPLE, allowing for future comparison to genomic data. Fresh prostates are collected from theatre, inked and sliced according to the previously published method. Additionally, coronal and axial mp-MRI images are utilised to calculate the desired position of the transverse slice and tissue punch, to accurately target tumour and benign areas. Non-dissociated tissue is cultured ex vivo for 72 hrs on gelatin sponges soaked in experimental drugs and drug combinations. Ex vivo cultures will be used to assess the effects of compounds on proliferation and cell signalling.

Results

The utilisation of mp-MRI data improves allows consistently accurate sampling of fresh prostate cancer specimens. Ex vivo culture in synthetic androgens, anti-androgens and/or kinase inhibitors, causes a change in proliferation compared to control treated tissue.

Conclusion

We have demonstrated that mp-MRI-based identification of tumour and benign tissue improves fresh tissue sampling for prostate cancer. Our ex vivo culture method in non-dissociated tissue will augment current pre-clinical drug development by offering a true-to-life model to assess drug efficacy and biomarkers of response to therapy.