Pre-clinical models enabling drug and biomarker discovery
Research theme lead: Prof Catrin Pritchard
Academic research theme members:
- Prof Karen Brown
- Prof Martin Dyer
- Dr Sam Khan
- Dr Esther Moss
- Dr Alessandro Rufini
- Prof Anne Thomas
- Dr Cristina Tufarelli
The Explant Facility at the University of Leicester aims to leverage the potential of patient-derived explants (PDEs) in the drug discovery pipeline via the ex vivo culture of live fragments of freshly resected human tumours that retain the histological features of original tumours.
Preclinical 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. Together with Marion MacFarlane from the MRC, we have pioneered an innovative patient-derived explant (PDE) platform that contextually preserves the tumour architecture necessary for drug testing and biomarker validation. The predictive power of PDEs has been extensively demonstrated, and incorporation of the spatial profiling of endpoint biomarkers using multi-immunofluorescence imaging uniquely allows responses within the tumour microenvironment to be monitored, including the efficacy of immunotherapies. This ground-breaking research has attracted considerable investment from translational, charity and commercial partners (CRUK-Therapeutic Discovery Laboratories, Pfizer, LifeArc, Breast Cancer Now, Hope Against Cancer). Underpinning the explant programme is a four-way agreement between the University of Leicester, MRC, LifeArc and CRUK-TDL.
Explants are a key platform for informing important go/no go decisions including:
- Drug responses of freshly resected tumour tissue to generate cell viability data
- Biomarker expression, pre- and post- drug treatment.
- Immune-cell phenotyping in PDEs to investigate drug effects on the immune system and tumour microenvironment
- Spatial analysis of multiple cell types.