Powley et al.pdf (2.03 MB)
Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery
journal contribution
posted on 2020-04-30, 08:29 authored by IR Powley, M Patel, G Miles, H Pringle, L Howells, A Thomas, C Kettleborough, J Bryans, T Hammonds, M MacFarlane, C PritchardPreclinical models that can accurately predict outcomes in the clinic are much sought after in the field of cancer drug discovery and development. Existing models such as organoids and patient-derived xenografts have many advantages, but they suffer from the drawback of not contextually preserving human tumour architecture. This is a particular problem for the preclinical testing of immunotherapies, as these agents require an intact tumour human-specific microenvironment for them to be effective. In this review, we explore the potential of patient-derived explants (PDEs) for fulfilling this need. PDEs involve the ex vivo culture of fragments of freshly resected human tumours that retain the histological features of original tumours. PDE methodology for anti-cancer drug testing has been in existence for many years, but the platform has not been widely adopted in translational research facilities, despite strong evidence for its clinical predictivity. By modifying PDE endpoint analysis to include the spatial profiling of key biomarkers by using multispectral imaging, we argue that PDEs offer many advantages, including the ability to correlate drug responses with tumour pathology, tumour heterogeneity and changes in the tumour microenvironment. As such, PDEs are a powerful model of choice for cancer drug and biomarker discovery programmes.
Funding
This research was supported and funded by the Explant Consortium comprising four partners: The University of Leicester, The MRC Toxicology Unit, Cancer Research UK Therapeutic Discovery Laboratories and LifeArc. Additional support was provided by the CRUK-NIHR Leicester Experimental Cancer Medicine Centre (C10604/A25151). Funding for Gareth Miles was provided by Breast Cancer Now’s Catalyst Programme (2017NOVPCC1066), which is supported by funding from Pfizer.
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Citation
British Journal of Cancer, 2020, 122, 735–744Author affiliation
College of Life SciencesVersion
- VoR (Version of Record)
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British Journal of CancerVolume
122Pagination
735–744Publisher
Springer Natureissn
0007-0920eissn
1532-1827Acceptance date
2019-11-15Copyright date
2020Available date
2020-01-02Publisher DOI
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https://www.nature.com/articles/s41416-019-0672-6#Abs1Spatial coverage
EnglandLanguage
engUsage metrics
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