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Accepted version GO PDE methods paper with tables and figures.pdf (1.6 MB)

Development of a patient-derived explant model for prediction of drug responses in endometrial cancer

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journal contribution
posted on 2021-01-20, 12:47 authored by A Collins, GJ Miles, IR Powley, R Hew, JH Pringle, M MacFarlane, C Pritchard, EL Moss
Objective
To undertake a pilot study to develop a novel Patient-Derived-Explant (PDE) model system for use in endometrial cancer (EC) that is capable of monitoring differential drug responses in a pre-clinical setting.

Methods
Fresh tumour was obtained post-hysterectomy from 27 patients with EC. Tumours were cut into 1–3 mm3 explants that were cultured at the air-liquid interface for 16–24 h in culture media. Explants were cultured in different media conditions to optimise viability. Explants were also treated with carboplatin/paclitaxel or pembrolizumab for 24 h and processed into histology slides. Multiplexed immunofluorescence for Ki67 (proliferation marker), cPARP (apoptosis marker) and CAM 5.2 (tumour mask) was performed followed by image analysis and quantitation of biomarker expression.

Results
EC samples are amenable to PDE culture with preserved histological architecture and PDE viability for up to 48 h, with the addition of autologous serum in culture media facilitating EC-PDE viability. Our PDE platform provides evidence of differential drug-response to conventional chemotherapeutics and immune checkpoint inhibition, and these responses can be assessed in the context of a preserved tumour microenvironment.

Conclusions
Our PDE platform represents a rapid, low-cost pre-clinical model which can be easily integrated into drug development pipelines. PDE culture preserves original tumour architecture and enables evaluation of spatial relationships in the tumour microenvironment. PDE culture has the potential for personalised drug-testing in a pre-clinical setting which is increasingly important in an era of personalised medicine in the treatment of EC.

History

Author affiliation

Leicester Cancer Research Centre, University of Leicester

Version

  • AM (Accepted Manuscript)

Published in

Gynecologic Oncology

Publisher

Elsevier BV

issn

0090-8258

eissn

1095-6859

Acceptance date

2020-11-27

Copyright date

2020

Available date

2021-12-10

Language

en

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