Introduction: The first cancer biomarker was described in 1848 when the presence of immunoglobulin light chains in urine was identified in 75% of patients with multiple myeloma. Circulating tumour DNA fragments (ctDNA) contain identical genetic defects to those seen in the primary tumour and because ctDNA fragments are released from all parts of the tumour ctDNA is a liquid biopsy. Advances in molecular technology have resulted in the development of new techniques enabling the detection of DNA molecules in body fluids such as blood, cerebrospinal fluid and urine.
Methods: ctDNA can be detected and monitored using specific assays for tumour and patient specific mutations or by using de novo sequencing looking for a broader range of mutations. Methodologies include novel sequencing technologies, massively parallel sequencing, highly sensitive quantitative polymerase chain reaction (PCR) testing, digital PCR and BEAMing (beads, emulsions, amplification and magnetics) digital PCR.
Results: This approach can be used to monitor disease burden following curative cancer surgery or neoadjuvant therapy. ctDNA is a potential marker of residual disease after surgery and the changes of ctDNA in response to treatment is consistent across all tumour types studied. Levels of ctDNA correspond with the clinical course and ctDNA increases with disease progression and correspondingly decreases with response to therapy. ctDNA can also be used to monitor the development of resistance to therapy during treatment. This has been demonstrated for leukaemia, lung cancer, bowel cancer and malignant melanoma. Data will be presented showing the application of ctDNA in patient care.
Conclusion: The implementation of new technologies has enabled the detection of ctDNA in blood in a clinical diagnostic setting and patients can now be monitored over time to assist in the assessment of response to treatment. The testing is specific to each individual’s tumour and forms part of personalised medicine.