NAB (Nucleic Acids Biomarker) Team
Background and Rationale of the NAB Team and Blood Borne Biomarkers
It is now well established that both tumour cells and tumour molecules are often present in cancer patient’s blood giving rise to the concept of using a simple blood sample as a ‘liquid biopsy’ to help monitor and improve patient care. Since circulating tumour cells (CTCs), tumour DNA (ctDNA) and circulating RNA are only present in blood at vanishingly low levels there are considerable technological challenges to overcome before sequence information from CTCs or ctDNA can be used to guide therapy. Dr Ged Brady joined CEP group in 2011 to lead the Nucleic Acids Biomarker (NAB) with the specific aim of overcoming the technical challenges by developing and applying practical oncology biomarkers from blood that will eventually benefit clinical practice and patient outcome. Previously he spent over 37 years developing advanced molecular biological methods and using them to further the understanding of a variety of key biological subjects including DNA replication control, cancer initiation and stem cell regulation. In the course of his scientific career he has carried out research in the Max Planck Institute for Molecular Biology (BERLIN), the German Cancer Research Centre (HEIDELBERG), the European Molecular Biology Laboratory (HEIDELBERG), the Ontario Cancer Institute (TORONTO) and the University of Manchester (UK) where he held positions of Lecturer and AstraZeneca Special Fellow. Prior to joining CEP, he was Research Director at the biotech company Epistem which was spun out from the CRUK MI (then known as the Paterson Institute for Cancer Research) by Prof Chris Potten (former acting Director of the Paterson Institute for Cancer Research). The move to CEP was prompted by a longstanding scientific and personal connection with Prof Dive stretching back to the early 1990s and the realisation that the combination of his molecular skills and the excellent clinical/research interface that Prof Dive has built up, provided a unique opportunity for him to develop practical blood borne biomarkers which may improve patient treatment.
Summary of Blood Borne Biomarker Approach and Highlights
Unlike use of standard biopsies which require surgery the starting point for the ‘liquid biopsy’ approach used by the NAB team is a simple minimally invasive blood sample obtained by routine clinical blood collection. To ensure that blood samples remain intact during the journey from patient to laboratory thereby enabling the development of reliable cellular and molecular readouts the NAB team has tested and verified blood stabilisation agents. These studies have shown that inclusion of suitable stabilisation agents in the blood collection tube enables transport of whole blood for up to 4 days at room temperature prior to analysis rather than requiring analysis within hours of blood draw when standard blood collection tubes are used. In addition to allowing worldwide transport of blood samples to CEP the NAB team has also shown that the same blood sample can be used for both CTC and ctDNA molecular analysis thereby minimising the amount of blood required. A routine blood analysis workflow has been developed by NAB which involves separation of the blood into plasma for isolation of ctDNA and cells for enrichment and isolation of CTCs. For CTC analysis the NAB team have put in place single cell isolation and whole genome amplification and have shown the utility of the approach in SCLC by the development of a potential CTC biomarker which may help predict patients who will respond to therapy. From the ctDNA obtained from the same sample used for CTC an efficient next generation sequencing (NGS) workflow has been established enabling detection of mutations in tumour DNA that may help personalise more effective treatment and monitor disease progression.
- Barbara Mesquita
- Deborah Burt
- Nigel Smith
- Franesca Chemi
- Jenny Antonello
- Chang Sik Kim
- Sakshi Gulati
- Anthony Chiu
- Fabiola Fernandez-Gutierrez