Measurement of genetically altered DNA shed from tumours into the circulation can potentially provide a new generation of blood-based cancer biomarkers. Compared with tissue DNA biomarkers which require surgery or biopsy, samples for circulating tumour DNA assays can be obtained with minimal inconvenience and at lower cost. Furthermore, in contrast to tissue, the use of circulating tumour DNA allows serial monitoring, faster delivery of results and potentially provides an integrative representation of genetic alterations across all tumour sites within a patient. In contrast to existing protein-based cancer biomarkers, all of which can be produced by benign disease, circulating tumour DNA biomarkers would be expected to be more specific for malignancy. Furthermore, unlike the available blood cancer biomarkers, circulating tumour DNA can be used to predict response to specific therapies, identify mechanisms of therapy resistance and detect potentially actionable mutations. One of the first circulating tumour DNA assays recommended for clinical use involves EGFR mutation testing for predicting response to EGFR tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer, especially when tumour tissue is unavailable. In order to accelerate the introduction of circulating tumour DNA assays into routine clinical use, laboratory medicine staff will have to undergo training in the use of polymerase chain reaction and DNA sequencing. Furthermore, existing circulating tumour DNA assays will need to be simplified, standardized, shown to have clinical utility, be made available at reasonable costs and be reimbursable.
Keywords: Cancer biomarker; circulating tumour DNA; liquid biopsy; predictive biomarker.