Leicester Cancer Research Centre

Liquid biopsy for detection and stratification of cancer

Research theme lead: Professor Jacqui Shaw

Academic research theme members

Cancer precision medicine has the potential to improve outcomes. When cancer cells die they can shed tiny amounts of DNA into the blood called circulating tumour DNA (or ctDNA). This can be sampled and analysed to facilitate early detection and monitoring of many cancers through a ‘liquid biopsy’. Additionally, tracking changes to this ctDNA may guide treatment strategies as tumours undergo temporal change. Current research is focussed on profiling of ctDNA and circulating tumour cells (CTCs) as a liquid biopsy of breast cancer and ctDNA profiling in thoracic, endometrial, pancreatic, and colorectal cancers.  

At Leicester, we are internationally recognised as leaders in the liquid biopsy field in breast and lung cancers including in the landmark TRACERx trial in non-small cell lung cancer (Jamal Hanjani et al, 2017; Abbosh et al, 2017). Our 2012 breast cancer study was the first to demonstrate the potential of ctDNA profiling to identify patients with dormant micrometastases who may go on to relapse (Shaw et al, 2012) and we were also first to show that detection of ESR1 gene mutations in ctDNA can predict resistance to aromatase inhibitor therapy (Guttery et al, 2015). We subsequently used next generation sequencing to compare ctDNA and individual circulating tumour cells in the same blood samples to capture tumour heterogeneity in metastatic disease (Shaw et al, 2017). More recently, working with Imperial College and Natera we demonstrated that personalised ctDNA profiling can detect breast cancer metastasis (molecular relapse) up to 2 years earlier than imaging providing a possible window for therapeutic intervention (Coombes et al, 2019).  

Within the theme, there is considerable expertise in assay validation for clinical utility.  

Prof Shaw led on the ctDNA pilot study for the 100K genomes project with Genomics England, which piloted comparison of different ctDNA technologies.  Building on these results, we are currently using ctDNA profiling to analyse patient samples from a number of different clinical studies and trials and working towards implementation of protocols to test patient samples in real time to detect resistance and relapse. 

Recognition of the need for service provision within the cfDNA Leicester-based hub, led to development of the Leicester Molecular Diagnostics Facility which offers numerous NGS-based testing services.

Research theme members

Dr Karen Page; Dr Caroline Cowley;   

 

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