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2024 Demetriou et al An optimised patient-derived explant platform for breast cancer reflects clinical responses to chemotherapy and antibody-directed therapy.pdf (1.77 MB)

An optimised patient-derived explant platform for breast cancer reflects clinical responses to chemotherapy and antibody-directed therapy

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posted on 2024-06-28, 10:37 authored by Constantinos Demetriou, Naila Abid, Michael Butterworth, Larissa Lezina, Pavandeep Sandhu, Lynne Howells, Ian R Powley, James H Pringle, Zahirah Sidat, Omar Qassid, Dave Purnell, Monika Kaushik, Kaitlin Duckworth, Helen Hartshorn, Anne Thomas, Jacqui A Shaw, Marion MacFarlane, Catrin Pritchard, Gareth J Miles

Breast Cancer is the most common cancer among women globally. Despite significant improvements in overall survival, many tumours are refractory to therapy and so novel approaches are required to improve patient outcomes. We have evaluated patient-derived explants (PDEs) as a novel preclinical platform for breast cancer (BC) and implemented cutting-edge digital pathology and multi-immunofluorescent approaches for investigating biomarker changes in both tumour and stromal areas at endpoint. Short-term culture of intact fragments of BCs as PDEs retained an intact immune microenvironment, and tumour architecture was augmented by the inclusion of autologous serum in the culture media. Cell death/proliferation responses to FET chemotherapy in BC-PDEs correlated significantly with BC patient progression-free survival (p = 0.012 and p = 0.0041, respectively) and cell death responses to the HER2 antibody therapy trastuzumab correlated significantly with HER2 status (p = 0.018). These studies show that the PDE platform combined with digital pathology is a robust preclinical approach for informing clinical responses to chemotherapy and antibody-directed therapies in breast cancer. Furthermore, since BC-PDEs retain an intact tumour architecture over the short-term, they facilitate the preclinical testing of anti-cancer agents targeting the tumour microenvironment.

Funding

Preclinical evaluation of drug efficacy using patient-relevant breast explant models: a bench-to-bedside approach

Breast Cancer Now

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CRUK-NIHR Leicester Experimental Cancer Medicine Centre (C10604/A25151)

Hope Against Cancer

National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre (BRC)

History

Author affiliation

College of Life Sciences Genetics & Genome Biology Professional Services

Version

  • VoR (Version of Record)

Published in

Scientific Reports

Volume

14

Issue

1

Pagination

12833

Publisher

Springer Science and Business Media LLC

issn

2045-2322

eissn

2045-2322

Copyright date

2024

Available date

2024-06-28

Spatial coverage

England

Language

en

Deposited by

Dr Gareth Miles

Deposit date

2024-06-26

Data Access Statement

The datasets generated and used during the current study are available from the corresponding author on reasonable request.

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