Circulating biomarkers

The BRC has a strong track record of investigating and validating blood-based biomarkers and subsequently in establishing their clinical utility.

Researcher holding a tray of biomarkers

We are pursuing NGS and digital PCR approaches to analyse circulating tumour DNA. In advanced cancers we will use serial blood-based analyses of circulating tumour DNA (ctDNA) to evaluate tumour inter- and intra-patient heterogeneity and study the adaptation of tumours to therapeutic pressure.

We will establish the clinical utility of ctDNA screening for mutation diagnosis in advanced cancer, assessing the potential of ctDNA screening to replace tumour biopsy in contemporaneously acquired tumour biopsies and plasma tumour DNA, and in large randomised clinical trials we will establish the potential of assaying plasma DNA as the sole predictive biomarker.

In early cancer we have demonstrated proof-of-principle that ctDNA can be used to detect minimal residual disease, and we will greatly expand this work with prospective studies to establish the potential of ctDNA analysis in predicting reoccurrence, with the aim of opening up an entirely new approach to patient selection for adjuvant therapy for solid tumours. We have a number of studies funded in this area, for example in lung, breast, prostate and GI cancers.

We have shown that whole-blood mRNA expression profiling provides information on the inflammatory anti-tumour response and thereby patient outcome. We will extend this work to pursue the development of blood-based predictive biomarkers for immunotherapeutic strategies through analyses of pre-treatment and serial post-treatment whole blood expression profiles, including the analysis of exosome RNA profiles.

Overall, we envisage that these blood based biomarkers may serve multiple purposes, serving as prognostic, predictive, pharmacodynamics and potentially intermediate endpoints of clonal disease responses.