Circulating Tumor DNA as a Cancer Biomarker: Fact or Fiction?

Abstract

The notion of utilizing cell-free DNA (cfDNA)8 in the circulation as a surrogate biomarker is not a novel concept. Mandel and Metais identified the presence of cfDNA in the blood of healthy individuals almost 60 years ago. Decades later, multiple groups were able to extend the work of Mandel and Metais into the identification of tumor-derived cfDNA—also known as circulating tumor DNA (ctDNA)—in the blood of cancer patients. These findings suggested that a “liquid biopsy” may be a feasible clinical tool because tumors seem to release fragments of DNA into the circulatory system that are both detectable and specific to the tumor. In the past decade, we have witnessed a surge in both new technologies and improvements on existing technologies for sequencing DNA that have made this once-laborious process cheaper and faster. In 2009, the cost of sequencing per genome was $100 000, whereas in 2014, this cost dropped to $5000 (taking into account labor, administration, management, utilities, reagents, and consumables). As a result, the use of ctDNA as a liquid biopsy has become ever more feasible. Clinically speaking, a ctDNA-based liquid biopsy would be the optimal mode of cancer management owing to various advantages including: ( a ) Retrieval of ctDNA would be minimally invasive especially compared to a tissue biopsy; ( b ) ctDNA could provide a full representation of the tumor (as well as any clonal metastases); and ( c ) ctDNA would provide a personalized snapshot of the patient's disease. Although the clinical use of ctDNA as a surrogate biomarker is still hampered by biological and technological hurdles, the implications of a liquid biopsy could be enormous as there would be numerous potential applications including (but not limited to): early detection, monitoring of minimal residual disease (MRD), assessment of treatment response, and triaging based on risk of recurrence. In this Q&A …